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genetics & genomics: What's the difference? Biopharmaceutical
best practices, lessons learned & ongoing challenges
adverse drug reaction ADR:
ADRs may include
drug interactions as one of many causes but the reverse is not true. The reader
is cautioned regarding usage of drug reaction terms as multiple nearly- similar
terms of varying granularity abound. .. "An adverse reaction to a drug has
been defined as any noxious or unintended reaction to a drug that is
administered in standard doses by the proper route for the purpose of
prophylaxis, diagnosis, or treatment(2). However, WHO's original definition of
ADR excluded therapeutic failures, intentional and accidental poisoning and drug
abuse, as well as adverse events due to medication errors such as drug
administration or non- compliance(1) ... Due to non- uniform usage of these
terms, it is sometimes difficult to compare various studies and derive incidence
rates, etc. for ADRs, and Drug Interactions. Saeed A Khan, "Drug
Interaction or Adverse Drug Reaction? Confusing Terms", British Medical
Journal 10 July, 1998 http://bmj.com/cgi/eletters/316/7149/1930
Alternatively: ADE
Adverse Drug Event
adaptive
clinical trials: The pharma
industry is gradually coming to realize that the classically structured clinical
trial does not offer enough flexibility to make use of continuously emerging
knowledge that is generated as the trial progresses. Unacceptable levels of
attrition in the clinical stage of development are driving profound changes in
the architecture, design, and analysis of clinical trials. The majority of
respondents to our survey said that reduction in patient numbers, less exposure
to study drug, and drops in overall trial duration were key points in favor of
adaptive designs; however, a majority also had specific concerns with adaptive
trials―concerns that involved methodological, logistical, and regulatory
uncertainties: Herman Mucke, Adaptive
Clinical Trials: Innovations in clinical trial design, management and analysis,
Insight Pharma Reports, 2007 ADMET
Administration, Dosage, Metabolism, Elimination, Toxicology:
We know a lot about A and M, not so much about D and E.
AITrends: Business and Technology of Enterprise
Artificial Intelligence
https://www.aitrends.com/ alternative
splicing:
The production of two or more
distinct mRNAs from RNA transcripts having the same sequence via differences in
splicing (by the choice of different exons). Mouse Genome Informatics http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=glossaryIndex&print=no
Recent
genome- wide analyses of alternative splicing indicate that 40- 60% of human
genes have alternative splice forms, suggesting that alternative splicing is
one of the most significant components of the functional complexity of the
human genome. Here we review these recent results from bioinformatics studies,
assess their reliability and consider the impact of alternative splicing on
biological functions. Although the 'big picture' of alternative splicing that
is emerging from genomics is exciting, there are many challenges. High-
throughput experimental verification of alternative splice forms, functional
characterization, and regulation of alternative splicing are key directions
for research. B. Modrek, C. Lee, "A genomic view of alternative
splicing" Nature Genetics30 (1) :13- 19, Jan. 2002 analyte specific
reagents: antibodies, both polyclonal and
monoclonal, specific receptor proteins, ligands, nucleic acid sequences, and
similar reagents which, through specific binding or chemical reaction with
substances in a specimen, are intended for use in a diagnostic application for
identification and quantification of an individual chemical substance or ligand
in biological specimens. CFR Title 21 Wikipedia
https://en.wikipedia.org/wiki/Analyte-specific_reagent See also
Laboratory Developed Tests antisense
(molecule): An oligonucleotide or analog
thereof that is complementary to a segment of RNA or DNA and that binds to it
and inhibits its normal function. IUPAC Medicinal Chemistry Molecular biologists
describing DNA sequences or referring to one of the two strands of double-
stranded DNA frequently use complementary pairs of terms, such as coding/ non-
coding, sense/ nonsense or transcribing/ non- transcribing. Unfortunately none
of these pairs is defined in a universally accepted way…Of the three pairs of
terms mentioned, NC- IUB and JCBN believe coding/ non- coding to be preferable.
Moreover, as the word 'coding' refers to the relationship between nucleic acids
and proteins, rather than the mere transcription of DNA into RNA, it is logical
to call the strand with the mRNA sequence the coding strand, as in the first
example. When DNA sequences are described by giving the sequence of only one
strand, this is usually the strand with the same sequence as the RNA (messenger,
ribosomal, transfer, etc.) and should therefore be called the coding strand.
[JCBN/ NC- IUB Newsletter, Joint Commission on Biological Nomenclature and
Nomenclature Commission of IUB 1989 http://www.chem.qmul.ac.uk/iubmb/newsletter/misc/DNA.html
Narrower terms: antisense DNA, antisense oligonucleotides, antisense RNA.
Related terms: RNAi; missense mutation, nonsense mutation; ribozymes antisense DNA:
DNA
that is complementary to the sense strand. (The sense strand has the same
sequence as the mRNA transcript. The antisense strand is the template for mRNA
synthesis.) Synthetic antisense DNAs are used to hybridize to complementary
sequences in target RNAs or DNAs to effect the functioning of specific genes for
investigative or therapeutic purposes. MeSH, 1991
antisense
oligonucleotides: Short fragments of DNA
or RNA that are used to alter the function of target RNAs or DNAs to which they
hybridize. MeSH, 1991
An oligonucleotide that
has a complementary sequence to a portion of, or to all of, an mRNA. Being
complementary to a particular target mRNA, antisense oligonucleotides bind
specifically to that mRNA; the proprietary chemical modifications made to the
antisense molecules facilitate tight binding. When binding occurs, the ability
of the mRNA to be read by the cell’s translational machinery is inhibited, and
synthesis of the protein that it encodes is blocked. Unlike a gene knockout,
this inhibition requires the continuous presence of the antisense molecule;
thus, it is reversible. A great advantage of antisense technology is that
researchers can design specific inhibitors of a gene of interest based only on
knowledge of the gene sequence. apoptosis:
One
of the two mechanisms by which CELL DEATH occurs (the other being the
pathological process of NECROSIS). Apoptosis is the mechanism responsible for
the physiological deletion of cells and appears to be intrinsically
programmed. It is characterized by distinctive morphologic changes in the
nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the
endonucleolytic cleavage of genomic DNA (DNA FRAGMENTATION) at internucleosomal
sites. This mode of cell death serves as a balance to mitosis in regulating the
size of animal tissues and in mediating pathologic processes associated with
tumor growth. MeSH, 1993 If someone could figure
out how to make fat cells undergo apoptosis (without harmful side effects) they
could make a bundle. Related terms: programmed cell death
artificial intelligence (AI): Theory
and development of COMPUTER SYSTEMS which perform tasks that normally
require human intelligence. Such tasks may include speech recognition,
LEARNING; VISUAL PERCEPTION; MATHEMATICAL COMPUTING; reasoning, PROBLEM
SOLVING, DECISION-MAKING, and translation of language. Year introduced:
MeSH 1986
Or as some people have noted, laboriously
trying to get computers to do what people do intuitively, without great
effort. Conversely there are things computer can do (relatively)
effortlessly such as massive numbers of error- free calculations.
The most promising applications seem to involve incorporating both
computer aided consideration of many possibilities, combined with human
judgment. Narrower
terms: artificial general intelligence, artificial narrow intelligence,
cellular automata, expert systems, fuzzy logic, genetic algorithms, neural
nets Related terms: augmented intelligence, training sets.
attrition
Early attrition of poor drug candidates is central to the new drug discovery
paradigm. Better to kill compounds before moving them into expensive
clinical trials.
augmented intelligence:
As
artificial intelligence (AI) grows more powerful, it can enable new
solutions to these systemic [health] issues. … Better described as
augmented intelligence, AI uses machine learning to rapidly analyze a
range of environmental, behavioral and clinical data to generate insights.
By using computational neural networks, it will someday be possible to use
big data to quickly identify causal linkages between specific
evidence-based treatments and improved patient outcomes. Nearer term, AI
has a critical role to play in improving the efficiency of health care
delivery and drug development. … by mining large volumes of clinical data
quickly, AI can also help physicians make better evidence-based treatment
decisions, especially in therapy areas where the standard of care is
changing rapidly.
Meanwhile, for the
life sciences industry AI’s main draw is its potential to tackle ongoing
R&D productivity challenges. AI analytics and predictive simulations can
improve the drug development failure rate by offering an in silico screen
to better understand which targeted interventions are likely to succeed or
fail. By narrowing the funnel of drug candidates earlier, companies can
begin to streamline research costs, while biasing human studies for
success. AI can also improve the efficiency of clinical trials, enabling
more targeted patient recruitment to reduce enrolment times, and, through
adaptive behavioral analytics, increasing both patient compliance and
retention. EY, What’s the right dose of AI to revitalize healthcare?
https://betterworkingworld.ey.com/digital/what-s-the-right-dose-of-ai-to-revitalize-health-care
Bayesian
statistics: Bayesian
statistics is an approach for learning from evidence as it accumulates. In
clinical trials, traditional (frequentist) statistical methods may use
information from previous studies only at the design stage. Then, at the data
analysis stage, the information from these studies is considered as a complement
to, but not part of, the formal analysis. In contrast, the Bayesian approach
uses Bayes’ Theorem to formally combine prior information with current
information on a quantity of interest. The Bayesian idea is to consider the
prior information and the trial results as part of a continual data stream, in
which inferences are being updated each time new data become available.
big
pharmas: MedAdNews
publishes an annual list of the top 50 pharmaceutical companies each fall.
"Biotech" companies such as Amgen are bigger than some pharmas.
biobank:
A type
of biorepository that
stores biological samples (usually human) for use in research
Wikipedia
https://en.wikipedia.org/wiki/Biobank
bioelectronics: the
field of developing medicines that use electrical impulses to modulate the
body's neural circuits. Virtually all of the body's organs and functions
are regulated through circuits of neurons communicating through electrical
impulses. The theory is that if you can accurately map the neural
signatures of certain diseases, you could then stimulate or inhibit the
malfunctioning pathways with tiny electrodes in order to restore health,
without having to flood the system with molecular medicines. Electroceuticals
swapping drugs for devices, Wired 28 May 2013
http://www.wired.co.uk/news/archive/2013-05/28/electroceuticals Related
term: electroceuticals; Genomics optogenetics
bioengineering:
The application of a systematic, quantitative, and
integrative way of thinking about and approaching the solutions of problems
important to biology, medical research, clinical proactive, and population
studies. The NIH Bioengineering Consortium agreed on the following definition
for bioengineering research on biology, medicine, behavior, or health
recognizing that no definition could completely eliminate overlap with other
research disciplines or preclude variations in interpretation by different
individuals and organizations. Integrates physical, chemical, or mathematical sciences and engineering principles for the
study of biology, medicine, behavior, or health. It advances fundamental
concepts, creates knowledge for the molecular to the organ systems levels, and
develops innovative biologics, materials,
processes, implants, devices,
and informatics
approaches for the prevention, diagnosis, and treatment of disease, for patient
rehabilitation, and for improving health. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2227944/#!po=12.5000
bioinformatics:
Roughly, bioinformatics describes any use of computers to handle
biological information. In practice the definition used by most people is
narrower; bioinformatics to them is a synonym for "computational molecular
biology" - the use of computers to characterise the molecular components of
living things. [Damian Counsell, bioinformatics.org FAQ] http://bioinformatics.org/faq/#whatIsBioinformatics
See for tight and loose definitions of bioinformatics, and
information on how long the term has been used. Research, development
or application of computational tools and approaches for expanding the use of
biological, medical, behavioral or health data, including those to acquire,
store, organize, archive, analyze, or visualize such data. Biomedical
Information Science and Technology Initiative BISTI Bioinformatics at the NIH,
2000 http://www.bisti.nih.gov/
We have
coined the term Bioinformatics for the study of informatic processes in biotic
systems. Our Bioinformatic approach typically involves spatial, multi- leveled
models with many interacting entities whose behavior is determined by local
information. Theoretical Biology Group, Univ. of Utrecht, Netherlands, Paulien
Hogeweg Director http://www-binf.bio.uu.nl/
Original definition was
“the study of informatic processes in biotic systems” Paulien Hogeweg MIRROR
beyond MIRROR, puddles of LIFE, in Artificial Life, ed. C.G. Langton,
Addison Wesley, 297-316, 1988 [Nick Saville's homepage, Theoretical Biology and
Bioinformatics, Utrecht Univ., Netherlands, 1997 Alternatively
computational biology
biologics:
Biologics,
in contrast to drugs that are chemically synthesized, are derived from living
sources (such as humans, animals, and microorganisms). Most biologics are
complex mixtures that are not easily identified or characterized, and many
biologics are manufactured using biotechnology. Biological products often
represent the cutting- edge of biomedical research and, in time, may offer the
most effective means to treat a variety of medical illnesses and conditions that
presently have no other treatments available. About CBER, FDA, US
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm123340.htm
biological
markers: Measurable
and quantifiable biological parameters (e.g. specific enzyme concentration,
specific hormone concentration, specific gene phenotype distribution in a
population, presence of biological substances) which serve as indices for health
- and physiology related assessments, such as disease risk, psychiatric
disorders, environmental exposure and its effects, disease diagnosis, metabolic
processes, substance abuse, pregnancy, cell line development, epidemiologic
studies, etc. MeSH, 1989
1. Parameter that
can be used to identify a toxic effect in an individual organism and can be used
in extrapolation between species. 2. Indicator signalling an event or condition
in a biological system or sample and giving a measure of exposure, effect, or
susceptibility. IUPAC Tox
biological
products:
Biological
products include a wide range of products such as vaccines, blood and blood
components, allergenics, somatic cells, gene therapy, tissues, and recombinant
therapeutic proteins. The Center for Biologics Evaluation and Research (CBER) is
responsible for ensuring the safety and efficacy of the biological products.
http://www.fda.gov/BiologicsBloodVaccines/ResourcesforYou/HealthcareProviders/default.htm
See also biologics, biopharmaceutical
biomarker
guidelines: The
National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC)
charged the Biomarker Task Force to develop recommendations to improve the
decisions about incorporation of biomarker studies in early investigational drug
trials. The Task Force members reviewed biomarker trials, the peer-reviewed
literature, NCI and U.S. Food and Drug Administration (FDA) guidance documents,
and conducted a survey of investigators to determine practices and challenges to
executing biomarker studies in clinical trials of new drugs in early
development. This document provides standard definitions and categories of
biomarkers, and lists recommendations to sponsors and investigators for
biomarker incorporation into such trials. Our recommendations for sponsors focus
on the identification and prioritization of biomarkers and assays, the
coordination of activities for the development and use of assays, and for
operational activities. We also provide recommendations for investigators
developing clinical trials with biomarker studies for scientific rationale,
assay criteria, trial design, and analysis. Guidelines
for the Development and Incorporation of Biomarker Studies in Early Clinical
Trials of Novel Agents, Dancey JE, et. al, Clin
Cancer Res. 2010 Mar 9. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/20215558
biomarker/s:
The term “biomarker”, a portmanteau of “biological marker”, refers to a broad
subcategory of medical signs – that is, objective indications of medical state
observed from outside the patient – which can be measured accurately and
reproducibly. Medical signs stand in contrast to medical
biomathematics:
The application of mathematics to problems in biology
and medicine. An essential tool in fields such as population genetics, cellular
neurobiology, comparative genetics, biomedical imaging, pharmacokinetics, and
epidemiology. It plays an increasingly vital role in the effort to understand
diseases and disorders, and to improve therapies. Collection Development
Manual, National Library of Medicine, US 2004 http://www.nlm.nih.gov/tsd/acquisitions/cdm/subjects14.html
BioMEMS
Biological MicroElectro Mechanical Systems: Includes
micro & nano drug delivery, interface of nanoscience and tissue engineering,
microfluidics, and miniaturized total analysis systems (microTAS), biosensors,
innovations in mass spectrometry, and nanoscale imaging.
biomimetics:
An interdisciplinary field in materials science, ENGINEERING,
and BIOLOGY,
studying the use of biological principles for synthesis or fabrication of BIOMIMETIC
MATERIALS. MeSH 2003
There is a
need to develop the next generation of restorative materials and medical
implants. New avenues of scientific inquiry may enable the development of
biomaterials that are safe, reliable, "smart", long- lasting, and
perform ideally in their respective biological environments. ... Over the last
few years biomimetics and tissue engineering have emerged as a new vision in the
field of tissue and organ repair and restoration. Biomimetics and tissue
engineering are interdisciplinary fields that combine information from the study
of biological structures and their functions with physics, mathematics,
chemistry and engineering for the generation of new materials, tissues and
organs. These approaches can offer new ways of: (a) developing biological
solutions for future design and synthesis of composite materials such as bone,
cartilage, tendon, ligament, skin, dentin, enamel, cementum and periodontal
ligament; (b) replacing and assembling functional tissues and organs; and (c)
evaluating medical and dental implants. In the area of craniofacial, oral and
dental principles from biomimetics and tissue engineering are applied to
developing dental and facial implants, new polymers for guided tissue
regeneration used in treating periodontal disease and bone and connective tissue
defects, coral- based hydroxyapatite replicas for reconstruction of alveolar
ridges and other osseous defects, temporomandibular joint (TMJ) and other joint
prostheses, formation of bone matrix substitutes, and artificial replicas of
bone, skin, and mucosa. [National Institute of Dental Research, NIH, US,
Biomimetics and Tissue Engineering in the Restoration of Orofacial Tissues, RFA:
DE-98-009, June 19, 1998] http://grants.nih.gov/grants/guide/rfa-files/RFA-DE-98-009.html
biomolecular
materials:
The major program emphasis is the creation of robust, scalable, energy-relevant
materials and systems with emergent behavior that work with the extraordinary
effectiveness of molecules and processes of the biological world. Major thrust
areas include: understanding, controlling, and building complex hierarchical
structures by mimicking nature’s self- and directed-assembly approaches; design
and synthesis of environmentally adaptive, self-healing multi-component, e.g.,
inorganic, polymeric, and biological, materials and systems that demonstrate
energy conversion and storage capabilities found in nature; functional systems
with collective properties not achievable by simply summing the individual
components; biomimetic and/or bioinspired routes for the synthesis of energy
relevant materials, e.g., semiconductor and magnetic materials under mild
conditions; and development of science-driven tools and techniques for the
characterization of biomolecular and soft materials.
https://science.energy.gov/bes/mse/research-areas/biomolecular-materials/
biomolecular
screening:
The
term "biomolecular screening" became widely used in the late 1980's to
broadly describe a new and rapidly adopted process for lead identification in
drug discovery. This new process involved screening natural product
extracts and/or amassed compound collections, typically from pharmaceutical
companies, in a random, unbiased manner to identify novel modulators of
biological targets ... The screens encompassed bioassays that could be
cell-based or purely biochemical in nature, and the need to screen increasing
numbers of samples as time progressed, fostered the development of many new
assay formats. IUPAC Glossary of terms in Biomolecular Screening 2011 http://iupac.org/publications/pac/83/5/1129/
biopharmaceutical:
also known as a biologic(al) medical product, biological,[1] or biologic,
is any pharmaceutical
drug product manufactured in, extracted
from, or semisynthesized from biological sources.
Different from totally
synthesized pharmaceuticals, they
include vaccines, blood,
blood components, allergenics, somatic
cells, gene
therapies, tissues, recombinant
therapeutic protein, and living cells used
in cell
therapy. Biologics can be composed of
sugars, proteins, or nucleic acids or complex combinations of these substances,
or may be living cells or tissues. They (or their precursors or
components) are isolated from living sources—human,
animal, plant, fungal,
or microbial.
Terminology surrounding biopharmaceuticals varies between groups
and entities, with different terms referring to different subsets of
therapeutics within the general biopharmaceutical category. Some regulatory
agencies use the terms biological
medicinal products or therapeutic biological product to refer
specifically to engineered macromolecular products
like protein- and nucleic
acid-based drugs, distinguishing
them from products like blood, blood components, or vaccines, which are
usually extracted directly from a biological source.[2][3][4] Specialty
drugs, a recent classification of
pharmaceuticals, are high-cost drugs that are often biologics.[5][6][7] The European
Medicines Agency uses the term advanced
therapy medicinal products (ATMPs) for medicines for human use that
are "based on genes, cells, or tissue engineering",[8] including
gene therapy medicines, somatic-cell therapy medicines, tissue-engineered
medicines, and combinations thereof.[9] Within
EMA contexts, the term advanced therapies refers specifically to
ATMPs, although that term is rather nonspecific outside those contexts.
Wikipedia accessed 2018 March 1
https://en.wikipedia.org/wiki/Biopharmaceutical
See also biologics, biological products
biopolymers:
Macromolecules (including proteins, nucleic acids and
polysaccharides) formed by living organisms. IUPAC Compendium Broader
term: polymers
bioprinting:
A material transfer technique used for assembling biological material or cells
into a prescribed organization to create functional structures such as MICROCHIP
ANALYTICAL DEVICES, cell microarrays, or three dimensional anatomical
structures. MeSH 2013
New
manufacturing technologies under the banner of rapid prototyping enable the
fabrication of structures close in architecture to biological tissue. In their
simplest form, these technologies allow the manufacture of scaffolds upon which
cells can grow for later implantation into the body. A more exciting prospect is
the printing and patterning in three dimensions of all the components that make
up a tissue (cells and matrix materials) to generate structures analogous to
tissues; this has been termed bioprinting.
Printing
and prototyping of tissues and scaffolds.
Derby B. Science. 2012 Nov
16;338(6109):921-6. doi: 10.1126/science.1226340 http://www.ncbi.nlm.nih.gov/pubmed/23161993
biorobotics:
Our research focuses on the role of sensing and mechanical design in motor
control, in both robots and humans. This work draws upon diverse disciplines,
including biomechanics, systems analysis, and neurophysiology. The main approach
is experimental, although analysis and simulation play important parts. In
conjunction with industrial partners, we are developing applications of this
research in biomedical instrumentation, teleoperated robots, and intelligent
sensors. Harvard Biorobotics Laboratory http://biorobotics.harvard.edu/
biotechnology: The integration of natural sciences and engineering sciences in order to achieve
the application of organisms, cells, parts thereof and molecular analogues
for products and services. IUPAC Compendium biotechnology firms:
The congressional Office of Technology concluded in its pathbreaking 1984 report, and emphasized even more strongly in another 1991
report, that "biotechnology" is not an industrial sector, but rather a set of methods useful in many industrial sectors (usually
established ones such as drugs and biologics, devices, or agriculture), but also for some entirely new applications (e.g., DNA
forensics). Many firms, almost 1500 listed by the various online services, are called "biotechnology" firms because they are largely built
around technologies developed since 1980. These firms are generally competing in established markets, however, even when they
compete by using novel products, services, and technical approaches. Robert
Cooke- Deegan et. al., World Survey of Funding for Genomics Research: Final
Report to the Global Forum for Health Research and the World Health
Organization, September 2000 http://www.stanford.edu/class/siw198q/websites/genomics/finalrpt.htm
biotechnology industry:
The biotechnological innovations of the 1970’s took
until the 1990’s to integrate. "The Pharmaceutical Industry and the
Revolution in Molecular Biology: Exploring the Interactions between Scientific,
Institutional and Organizational Change, Iain M. Cockburn, Rebecca Henderson,
Scott Stern, 1999. http://www.cid.harvard.edu/cidbiotech/events/henderson.htm
Biotechnology
started as a means for producing biopharmaceuticals. It has only
relatively recently begun to be more integrated into the drug discovery and
development process.
blockbuster
drugs:
an extremely popular drug that generates annual sales of at least
$1 billion for the company that sells it. Examples of blockbuster drugs include
Vioxx, Lipitor and Zoloft.
https://www.investopedia.com/terms/b/blockbuster-drug.asp 90% of drugs
marketed by big pharma bring in less than $180 million per year. Compare that
number to the total cost of $350- 600 million for approving a single drug
(including all the failures that lead up to it). Of course, one might think that
the money can be made back in four years, but drugs have a huge maintenance cost
in terms of regulatory compliance, marketing and sales. The margin on a drug-
to- drug basis is very slim. This places the onus on the other 10% of drugs to
be blockbusters – to more than make up for most of the other drugs that are
earning far too little revenue. This is how the industry has structured itself
around a blockbuster mentality – a reliance on drugs that bring in at least
$500 million per year in revenue. Considering the odds of achieving blockbuster
status, this is a very high- risk strategy. Pharmaceutical companies will have
to change their ways if they are going to enter the new era of individualized
medicine.
borderline products:
Sometimes it may be unclear whether a particular product is a cosmetic product
under cosmetics legislation or whether it falls under other sectorial
legislation. In the case of these “borderline products”, the decision on a
product’s classification must be taken on a case-by-case basis.
European Commission, Cosmetics
https://ec.europa.eu/growth/sectors/cosmetics/products/borderline-products_en
bottom up:
The classical reductionist approach to biology which aims
to examine the smallest units to gain insight into the larger ones. Mendelian
genetics, which looks at single genes, is a bottom- up approach.
Compare
top- down brand name drug:
A
drug marketed under a proprietary, trademark- protected name. Glossary, Drugs@FDA,
CDER,
https://www.fda.gov/drugs/drug-approvals-and-databases/drugsfda-glossary-terms
cancer genome interpretation:
Much
promise exists in cancer precision medicine, in which the identification
of the specific mutations in a patient’s tumor allow doctors to tailor
appropriate treatments for individual patients. Unfortunately, cancer
precision medicine is not yet a reality for most cancer patients, because
we cannot fully interpret the clinical impact of the cancer genome. Broad
Institute
https://www.broadinstitute.org/cancer/cancer-genome-interpretation
CAR T-cell therapy: A
type of treatment in which a patient's T cells (a type of immune system
cell) are changed in the laboratory so they will attack cancer cells. T
cells are taken from a patient’s blood. Then the gene for a special
receptor that binds to a certain protein on the patient’s cancer cells is
added in the laboratory. The special receptor is called a chimeric antigen
receptor (CAR). Large numbers of the CAR T cells are grown in the
laboratory and given to the patient by infusion. CAR T-cell therapy is
being studied in the treatment of some types of cancer. Also called
chimeric antigen receptor T-cell therapy. NCI Dictionary of Cancer Terms
https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=771302
CBER Center for
Biologics Evaluation and Research:
CBER
is the Center within FDA that regulates biological products for human use under
applicable federal laws, including the Public Health Service Act and the Federal
Food, Drug and Cosmetic Act. CBER protects and advances the public health by
ensuring that biological products are safe and effective and available to those
who need them.
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/default.htm CDER Center for Drug
Evaluation and Research:
http://www.fda.gov/cder/
The Center
for Drug Evaluation and Research (CDER) performs an essential public health task
by making sure that safe and effective drugs are available to improve the health
of people in the United States. As part of the U.S. Food and Drug
Administration (FDA), CDER regulates over-the-counter and prescription drugs,
including biological therapeutics and generic drugs. This work covers more than
just medicines. For example, fluoride toothpaste, antiperspirants, dandruff
shampoos and sunscreens are all considered "drugs."
https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/default.htm
cDNA complementary
DNA:
A single stranded DNA molecule with
a nucleotide sequence that is complementary to an RNA molecule; cDNA is formed
by the action of the enzyme reverse transcriptase on an RNA template. After
conversion to the double stranded form, cDNA is used for molecular cloning or
for hybridization studies. [IUPAC Biotech]
A complementary DNA for
a messenger RNA molecule. Unlike an mRNA, a cDNA can be easily propagated and
sequenced. [NCBI]
Single-stranded
complementary DNA synthesized from an RNA template by the action of RNA-
dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not
cDNA) is used in a variety of molecular cloning experiments as well as serving
as a specific hybridization probe. MeSH, 1994 chaperome:
The
goal of the "All Chaperome" project is to characterize the molecular
chaperones of C. elegans. We have identified approximately 170
chaperones corresponding to the major classes of chaperones and co-chaperones
conserved in S. cerevisiae, and vertebrates. Taking advantage of the
lineage analysis of C. elegans, we are determining the expression
pattern of each chaperone gene to establish a basis for network interactions and
tissue specificity during development and aging. Morimoto Laboratory, All
Chaperome Project, 2007 http://www.biochem.northwestern.edu/ibis/morimoto/research/research_chap2.html
Thanks to Heike Aßmus, University of Rostock for alerting me to this -ome.
checkpoint inhibitors: Most
of the current excitement over cancer immunotherapy is focused on the
field of immune checkpoint inhibitors, a class of monoclonal antibodies
(MAbs) that inhibit pathways that block the response of T cells to
antigens. Checkpoint inhibitors work to overcome mechanisms by which
tumors co-opt certain immune checkpoint pathways, and thus resist T
cell-mediated antitumor immunity. Cancer Immunotherapy: Immune Checkpoint
Inhibitors, Cancer Vaccines, and Adoptive T-cell Therapies report, 2014 chemical genetics:
A "chemistry first" approach to drug discovery. Chemical genetics
strategies start with libraries of chemical compounds, and then screen these
libraries to find compounds that produce differences in a disease- relevant
phenotype. Once a phenotype modifying compound is found, it is used to identify
the particular target protein to which it binds in the cells or small model
organisms in which it had previously been studied. Sometimes used
interchangeably with "chemical genomics". "Chemical genetics
approach" first coined [by Rebecca Ward, at Harvard University] on the
inaugural cover of Chemistry and Biology nine years ago. Her term reminds us
that to understand a life process you should perturb it and determine the
consequence and that such an approach should strive to have the broad power and
generality of genetics. Stuart L. Schreiber, The Small Molecule Approach
to Biology, Chemical & Engineering News, March 3, 2003 http://www-schreiber.chem.harvard.edu/home/pdffiles/8109genomics.pdf
Alternatively/Related terms: biochemical genomics, chemical genomics,
chemogenomics, chemical proteomics
chemical
information:
Many people
view chemoinformatics as an extension of chemical information, which is a well
established concept covering many areas that employ chemical structures, data
storage and computational methods, such as compound registration databases, on-
line chemical literature, SAR analysis and molecule- property calculation.
Timothy Ritchie "Chemoinformatics; manipulating chemical information to
facilitate decision- making in drug discovery" Drug Discovery Today 6(16):
813-814, Aug. 2001
chemical
information system: Must include
registration, computed and measured properties, chemical descriptors and
inventory. The primary purpose is to be able to identify a chemical substance,
find compounds similar to the target compound and determine the location of the
compound. To effectively build it, an object definition of the chemical sample
is paramount…The hub [central database] of the chemical information system is
the inventory system. Frank Brown "Chemoinformatics: What is it and How
does it Impact Drug Discovery" Annual Reports in Medicinal Chemistry 33:
375-384, 1998 cheminformatics:
The practice of finding the "best-
fitting" compounds to address particular targets. The field encompasses
diversity analysis and library design, virtual screening, rational drug design,
and tools and approaches for predicting activity and other properties from
structure. Going by the numbers
in Google.com cheminformatics seems to be the currently most used form of
this word, overtaking chemoinformatics in about 2001.
Alternatively chemical informatics, chemical information,
chemi-informatics chemoinformatics:
Chemoinformatics is an integral part of the
discipline of knowledge management. Nicholas J. Hrib, Norton P.
Peet "Chemoinformatics: are we exploiting these new science?" Drug
Discovery Today 5 (11): 483- 485, Nov. 2000
Increasingly
incorporates "compound registration into databases, including library
enumeration; access to primary and secondary scientific literature; QSAR
Quantitative Structure Activity Relationships) and similar tools for relating
activity to structure; physical and chemical property calculations; chemical
structure and property databases, chemical library design and analysis;
structure- based design and statistical methods. Because these techniques have
traditionally been considered the realms of scientists from different
disciplines, differences in computer systems and terminology provide a barrier
to effective communication. This is probably the single most challenging problem
that chemoinformatics must solve. [M Hann and R Green "Chemoinformatics –
a new name for an old problem?" Current Opinion in Chemical Biology 3:379-
383, 1999]
Mixing
of information technology and management to transform data into information and
information into knowledge for the intended purpose of making better decisions
faster in the arena of drug lead identification and optimization. ..In
Chemoinformatics there are really only two [primary] questions: 1.) what to test
next and 2.) what to make next. The main processes within drug discovery are
lead identification, where a lead is something that has activity in the low
micromolar range, and lead optimization, which is the process of transforming a
lead into a drug candidate. [Frank Brown "Chemoinformatics: What is
it and How does it Impact Drug Discovery" Annual Reports in Medicinal
Chemistry 33: 375-384, 1998 chemotherapy:
Often refers to cancer treatments, but is also used
more generally for drug therapy.
Wikipedia
https://en.wikipedia.org/wiki/Chemotherapy
circulating tumor
cells CTCs:
Molecular
characterization of tumour material will become increasingly important in
selecting patients for clinical trials and offering appropriate treatment for
patients in clinical practice. Recent advances in the field have indicated that
the molecular characteristics of a tumour can be determined from circulating tumour
cells and
circulating tumour DNA; thus, a simple blood sample could provide these data in
a simple, convenient and efficient manner. Circulating
tumour-derived predictive biomarkers in oncology, Hodgson DR, Wellings R, Orr
MC, McCormack R, Malone M, Board RE, Cantarini MV., AstraZeneca, Drug Discovery
Today. 2010 Feb;15(3-4):98-101. Epub 2010 Jan 4. http://www.ncbi.nlm.nih.gov/pubmed/20045486
clinical
bioinformatics: Different
from other informatics, clinical bioinformatics should focus more on clinical
informatics, including patient complaints, history, therapies, clinical symptoms
and signs, physician's examinations, biochemical analyses, imaging profiles,
pathologies and other measurements. It was emphasized that the simultaneous
evaluation of clinical and basic research could improve medical care, care
provision data, and data exploitation methods in disease therapy and algorithms
for the analysis of such heterogeneous data sets. Clinical bioinformatics:
a new emerging science Xiangdong Wang and
Lance Liotta, Journal
of Clinical Bioinformatics 1:1 2011http://www.ncbi.nlm.nih.gov/
clinical
informatics:
The
application of informatics approaches to the clinical- evaluation phase of drug
development. These approaches can include clinical- trial simulations to improve
trial design and patient selection, as well as electronic capturing and storing
of clinical data and protocols. The goal is to reduce expenses and time to
market clinical
proteomics: Aims to discovery proteins with medical relevance said Alan
Sachs, a director of R&D at Merck. Such discoveries can be defined broadly
as those that identify a potential target for pharmaceutical development, a
marker(s) for disease diagnosis or staging and risk assessment, both for medical
and environmental studies. (Note that there is a difference between developing
biological insight and identifying clinically important diagnostic and
prognostic protein- based assays.) Defining the Mandate of Proteomics in the
Post- Genomics Era, Board on International Scientific Organizations, National
Academy of Sciences, 2002 http://www.nap.edu/books/NI000479/html/R1.html clone:
A population of genetically identical cells produced from
a common ancestor. Sometimes also used to refer to a number of recombinant
DNA molecules all carrying the same inserted sequence. IUPAC Medicinal
Chemistry, IUPAC Compendium Clone was coined by
Herbert J. Webber in 1903 for "a colony of organisms derived asexually from
a single progenitor" and was quickly adopted by botanists and cell
biologists. But the popular perception of cloning can be traced to Alvin
Toffler's Future Shock (1970) and was quickly popularized (and extended
to items such as computers). But Lee Silver, Professor of Molecular Biology and
Public Affairs, Princeton Univ. concludes that "the scientific community
has lost control over Webber's pleasant sounding little word. Cloning has a
popular connotation that is impossible to dislodge. We must accept that
democratic debate on cloning is bereft of any meaning. Science and Scientists
would be better served by choosing other words to explain advances in
developmental biotechnology to the public". L. Silver "What are
clones? They're not what you think they are" Nature 412 (6842): 21, 5 July
2001
cloning:
Using specialized DNA technology (see cloning vector) to
produce multiple, exact copies of a single gene or other segment of DNA to
obtain enough material for further study. This process is used by researchers in
the Human Genome Project, and is referred to as cloning DNA. The resulting
cloned (copied) collections of DNA molecules are called clone libraries.
A second type of cloning exploits the natural process of cell division to make
many copies of an entire cell. The genetic makeup of these cloned cells, called
a cell line, is identical to the original cell. A third type of cloning
produces complete, genetically identical animals such as the famous
Scottish sheep, Dolly. DOE The process of making
copies of a specific piece of DNA, usually a gene. When geneticists speak of
cloning, they do not mean the process of making genetically identical copies of
an entire organism. NHGRI Rooting plant cuttings
and having identical twins can also be considered types of cloning. collaboration:
Collaboration can
be horizontal (a group of small companies), vertical (suppliers and
customers), sectoral (same industry sector) or lateral (complementary but
different sectors). From the Latin, meaning to work with.
The biomedical
industry faces a crisis in productivity, with rapidly rising costs for
R&D but declining results. While many other industries have found ways
to enhance performance using pre-competitive collaboration, the biomedical
industry has been reluctant to embrace such sharing of information,
investments, risk and costs. There are, however, encouraging signs that
important shifts are taking place, as evidenced by a growing number of
consortia, programs for open innovation, and experiments with
crowd-sourcing to find solutions outside a single company. One area ripe
for collaboration is the field of neglected diseases, where the shortage
of traditional profit opportunities mean that companies are forced to
re-think how to achieve the most productive results.
combination products:
Include
(1) A product comprised of two or more regulated components, i.e., drug/device,
biologic/device, drug/biologic, or drug/device/biologic, that are physically,
chemically, or otherwise combined or mixed and produced as a single entity; (2) Two or more
separate products packaged together in a single package or as a unit and
comprised of drug and device products, device and biological products, or
biological and drug products; (3) A drug, device, or
biological product packaged separately that according to its investigational
plan or proposed labeling is intended for use only with an approved individually
specified drug, device, or biological product where both are required to achieve
the intended use, indication, or effect and where upon approval of the proposed
product the labeling of the approved product would need to be changed, e.g., to
reflect a change in intended use, dosage form, strength, route of
administration, or significant change in dose; or (4) Any investigational
drug, device, or biological product packaged separately that according to its
proposed labeling is for use only with another individually specified
investigational drug, device, or biological product where both are required to
achieve the intended use, indication, or effect. Definition of a Combination
Product, FDA, Office of Combination Products, As defined in 21
CFR § 3.2(e) http://www.fda.gov/CombinationProducts/AboutCombinationProducts/ucm118332.htm combination therapies:
As ever more
combination therapies are applied in various areas of medicine, there is a
growing need for quantitative descriptions of combination effects. While most of
the scientific community has agreed on a basic standard for synergy, there is no
consensus on quantifying the degree to which a combination may deviate from
synergy, and no predictive models are accepted to serve as benchmarks.
This project will convene a working group, involving leading experts on
combination effects, to (1) endorse the synergy criterion recommended at a
recent meeting in Finland, (2) adopt standard measures of combination effect to
quantify deviations from synergy, and (3) explore predictive combination-effect
models for multiply-inhibited biological interaction networks. Quantifying the
Effects of Compound Combinations Chemistry International 25 (4) July-Aug. 2004, http://www.iupac.org/publications/ci/2004/2604/pp5_2003-059-1-700.html combinatorial
chemistry: Using a combinatorial process to
prepare sets of compounds from sets of building blocks. IUPAC
Combinatorial Chemistry Related terms: combinatorial libraries, diversity, microtiter
plates, molecular diversity, fully combinatorial, pool/ split companion
diagnostics: A trend in genetic diagnostics and
therapeutics is for the two to become increasingly intertwined. Companion
diagnostics identify subsets of patients who would benefit from a specific
drug.
comparative
effectiveness research CER: the
direct comparison of existing health
care interventions to determine which work
best for which patients and which pose the greatest complex:
It has become common to use complicated and complex interchangeably … The
essence of ‘complicated’ is hard to figure out. ..Complex, on the other hand
is a term reserved for systems that display properties that are not predictable
from a complete description of their components, and that are generally
considered to be qualitatively different from the sum of their parts.
[Editorial, "Complicated is not complex" Nature Biotechnology 17: 511
June 1999 Would it be fair to say
that Mendelian genetics is linear, while genomics and polygenic diseases/traits
are nonlinear? According to the Oxford
English Dictionary one of the meanings of complicated is complex,
though it also means not easy to unravel or separate. Both complex and
complicated are contrasted with simple. Whatever the original senses of these
two words, the above distinction seems a useful one now. Related term:
complexity; Narrower terms: biocomplexity, complex diseases, complex genomes; complex
phenotypes, complex traits
complex diseases:
Diseases
characterized by risk to relatives of an affected individual which is greater
than the incidence of the disorder in the population.[NHLBI Are complex diseases
essentially the same as polygenic diseases? complex phenotypes:
Those
that exhibit familial clustering, which may mean that there is some genetic
component, but that do not occur in Mendelian proportions in pedigrees. Complex
phenotypes may be continuous in distribution, like height or blood pressure, or
they may be dichotomous, like affected and not affected. The complexity arises
from the fact one cannot accurately predict the expression of the phenotype from
knowledge of the individual effects of individual factors considered alone, no
matter how well understood each separate component may be. Genetic Architecture,
Biological Variation and Complex Phenotypes, PA-02-110, May 29, 2002- June 5,
2005 http://grants1.nih.gov/grants/guide/pa-files/PA-02-110.html
complex trait:
Has
a genetic component that is not strictly Mendelian (dominant, recessive, or sex
linked) and may involve the interaction of two or more genes to produce a
phenotype, or may involve gene environment interactions." NHLBI Related term:
genetic architecture
complexity::
Currently there are more than 30 different mathematical descriptions of
complexity. However we have yet to understand the mathematical dependency
relating the number of genes with organism complexity. J. Craig Venter et. al.
"The sequence of the Human Genome" Science 291 (5507): 1347, Feb. 16,
2001
An ill- defined term
that means many things to many people. Complex things are neither random nor
regular, but hover somewhere in between. Intuitively, complexity is a measure
of how interesting something is. Other types of complexity may be well
defined. Gary William Flake, Computational Beauty of Nature: Computer Explorations of
Fractals, Chaos, Complex Systems, and Adaptation, MIT Press, 1998 http://www.comdig.org/
compound
quality: Physicochemical
properties such as lipophilicity and molecular mass are known to have an
important influence on the absorption, distribution, metabolism, excretion
and toxicity (ADMET) profile of small-molecule drug candidates. To assess
the use of this knowledge in reducing the likelihood of compound related
attrition, the molecular properties of compounds acting at specific drug
targets described in patents from leading pharmaceutical companies during
the 2000-2010 period were analysed. ... we conclude that a
substantial sector of the pharmaceutical industry has not modified its
drug design practices and is still producing compounds with suboptimal
physicochemical profiles. Paul D. Leeson and Stephen A St-Gallay The
influence of the "organizational factor" on compound quality in
drug discovery, Nature Reviews Drug Discovery, 10:749-765, October 2011http://www.ncbi.nlm.nih.gov/pubmed/21959288
Computer-aided
detection (CADe),
also called computer-aided diagnosis (CADx),
are systems that assist doctors in the interpretation of medical images.
Imaging techniques in X-ray, MRI,
and ultrasound diagnostics
yield a great deal of information that the radiologist or other medical
professional has to analyze and evaluate comprehensively in a short time.
CAD systems process digital images for typical appearances and to
highlight conspicuous sections, such as possible diseases, in order to
offer input to support a decision taken by the professional. CAD
also has potential future applications in digital
pathology with the advent of whole-slide imaging and machine
learning algorithms. So far its application has been
limited to quantifying immunostaining but
is also being investigated for the standard H&E
stain.[1]
CAD is an interdisciplinary technology
combining elements of artificial
intelligence and computer
vision with radiological and pathology image
processing. A typical application is the detection of a tumor. For
instance, some hospitals use CAD to support preventive medical check-ups
in mammography (diagnosis
of breast cancer), the detection of polyps in the colon
and lung
cancer. Wikipedia accessed 2018 Feb 26
https://en.wikipedia.org/wiki/Computer-aided_diagnosis
computational
physiology: The International Union of Physiological
Sciences (IUPS) Physiome Project is an internationally collaborative open-
source project to provide a public domain framework for computational
physiology, including the development of modeling standards, computational tools
and web-accessible databases of models of structure and function at all spatial
scales [1,2,3]. It aims to develop an infrastructure for linking models of
biological structure and function across multiple levels of spatial organization
and multiple time scales. The levels of biological organisation, from genes to
the whole organism, includes gene regulatory networks, protein- protein and
protein- ligand interactions, protein pathways, integrative cell function,
tissue and whole heart structure- function relations. The whole heart models
include the spatial distribution of protein expression. Keynote: Peter J.
Hunter, Univ of Auckland, International Society of Computational Biology,
Detroit, MI, 2005 http://www.iscb.org/ismb2005/keynotes.html Copy Number
Polymorphisms CNPs: represent a greatly underestimated aspect of human genetic
variation. Recently, two landmark studies reported genome-wide analyses of CNPs
in normal individuals and represent the beginning of an understanding of this
type of large-scale variation. Patrick G. Buckley*,
Kiran K. Mantripragada*,
Arkadiusz Piotrowski, Teresita Diaz de Ståhl and Jan P. Dumanski Copy-number
polymorphisms: mining the tip of an iceberg, Trends in Genetics 21 (6): 315-
317, June 2005
Another term for CNV
Copy Number
Variation CNV: We defined a CNV as a DNA segment that
is 1kb or larger and present at variable copy number in comparison with a
reference genome. A CNV can be simple in structure, such as tandem duplication,
or may involve complex gains or losses of homologus sequences at multiple sites
in the genome. Richard Redon et. al, Global
Variaiton in copy number in the human genome, Nature 2006 Nov 23;444 (7118):
444- 454 Copy number variations
(CNVs) hold immense potential to explain genetic diversity, predict disease risk
and diagnose complex genomic disorders have long resisted understanding. Now
recently developed whole-genome scanning technologies have catalyzed the
appreciation of CNVs in the genomic community. Studies linking insertions,
deletions, and inversions to disease etiology continue to multiply. As
genome-wide scanning techniques become more prevalent in diagnostic
laboratories, the major challenge is how to interpret accurately which
variations are pathogenic in nature and which are benign.
CRISPR: “CRISPR”
(pronounced “crisper”) stands for Clustered Regularly Interspaced Short
Palindromic Repeats, which are the hallmark of a bacterial defense system
that forms the basis for CRISPR-Cas9 genome editing technology. In the
field of genome engineering, the term “CRISPR” or “CRISPR-Cas9” is often
used loosely to refer to the various CRISPR-Cas9 and -CPF1, (and other)
systems that can be programmed to target specific stretches of genetic
code and to edit DNA at precise locations, as well as for other purposes,
such as for new diagnostic tools. With these systems, researchers can
permanently modify genes in living cells and organisms and, in the future,
may make it possible to correct mutations at precise locations in the
human genome in order to treat genetic causes of disease. Other systems
are now available, such as CRISPR-Cas13’s, that target RNA provide
alternate avenues for use, and with unique characteristics that have been
leveraged for sensitive diagnostic tools, such as SHERLOCK. Questions &
Answers about CRISPR: What is CRISPR? , Broad Institute https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/questions-and-answers-about-crispr
Wikipedia https://en.wikipedia.org/wiki/CRISPR
Related terms: gene editing, genome editing
CRISPR/Cas9: Several
approaches to genome editing have been developed. A recent one is known as
CRISPR-Cas9, which is short for clustered regularly interspaced short
palindromic repeats and RISPR-associated protein 9. The CRISPR-Cas9
system has generated a lot of excitement in the scientific community
because it is faster, cheaper, more accurate, and more efficient than
other existing genome editing methods. What are genome
editing and CRISPR-Cas9? Genetics Home Reference, NIH NLM https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting
data quality:
A vital consideration for data analysis and interpretation.
While people are still reeling from the vast amount of data becoming available,
they need to brace themselves to both discard low quality data and handle much
more at the same time.
data science:
also known as data-driven science, is an interdisciplinary field of
scientific methods, processes, and systems to extract knowledge or
insights from data in
various forms, either structured or unstructured,[1][2]similar
to data
mining. … It employs techniques and
theories drawn from many fields within the broad areas of mathematics, statistics, information
science, and computer
science, in particular from the
subdomains of machine
learning, classification, cluster
analysis, data
mining, databases,
and visualization.
… is now often applied to business
analytics,[7] or
even arbitrary use of data, or used as a sexed-up term for statistics.[8] While
many university programs now offer a data science degree, there exists no
consensus on a definition or curriculum contents.[7 Wikipedia
accessed 2018 Jan 23 https://en.wikipedia.org/wiki/Data_science
data scientist: a
high-ranking professional with the training and curiosity to make
discoveries in the world of big data. The title has been around for only a
few years. (It was coined in 2008 by one of us, D.J. Patil, and Jeff
Hammerbacher, then the respective leads of data and analytics efforts at
LinkedIn and FaceBook.) … More
than anything, what data scientists do is make discoveries while swimming
in data. It’s their preferred method of navigating the world around them.
At ease in the digital realm, they are able to bring structure to large
quantities of formless data and make analysis possible. They identify rich
data sources, join them with other, potentially incomplete data sources,
and clean the resulting set.. … As they make discoveries, they communicate
what they’ve learned and suggest its implications for new business
directions. Often they are creative in displaying information visually and
making the patterns they find clear and compelling. … Data scientists’
most basic, universal skill is the ability to write code. ..More enduring
will be the need for data scientists to communicate in language that all
their stakeholders understand—and to demonstrate the special skills
involved in storytelling with data, whether verbally, visually,
or—ideally—both. … Data scientists want to be in the thick of a developing
situation, with real-time awareness of the evolving set of choices it
presents. Data Scientist: The Sexiest Job of the 21st Century Thomas H.
Davenport and D.J. Patil, Harvard Business Review Oct 2012 http://hbr.org/2012/10/data-scientist-the-sexiest-job-of-the-21st-century/ar/5
data stewardship: Beyond
proper collection, annotation, and archival, data stewardship includes
the notion of ‘long-term care’ of valuable digital assets, with the goal
that they should be discovered and re-used for downstream investigations,
either alone, or in combination with newly generated data.
The outcomes from good data management
and stewardship,
therefore, are high quality digital publications that facilitate and
simplify this ongoing process of discovery, evaluation, and reuse in
downstream studies.: The
FAIR Guiding Principles for Scientific Data Management
and Stewardship
Mark D Wilkinson, Madrid, Spain; Michel Dumontier, Stanford CA, Berend
Mons, Leiden Univ, Utrecht, Netherlands, https://www.nature.com/articles/sdata201618
deep learning:
another
hot topic buzzword – is simply machine learning which is derived from
“deep” neural nets. These are built by layering many networks on top of
each other, passing information down through a tangled web of algorithms
to enable a more complex simulation of human learning. Due to the
increasing power and falling price of computer processors, machines with
enough grunt to run these networks are becoming increasingly affordable.
What is Machine Learning: A complete beginner’s guide in 2017, Bernard
Marr, Forbes 2017 May
deep machine learning: Deep
machine learning (DML)
holds the potential to revolutionize machine learning by automating rich
feature extraction, which has become the primary bottleneck of human
engineering in pattern recognition systems. However, the heavy
computational burden renders DML systems implemented on conventional
digital processors impractical for large-scale problems. The highly
parallel computations required to implement large-scale deep learning
systems are well suited to custom hardware. Analog computation has
demonstrated power efficiency advantages of multiple orders of magnitude
relative to digital systems while performing nonideal computations. In
this paper, we investigate typical error sources introduced by analog
computational elements and their impact on system-level performance in
DeSTIN--a compositional deep learning architecture. On
the impact of approximate computation in an analog DeSTIN architecture. Young
S, Lu
J, Holleman
J, Arel
I. IEEE
Trans Neural Netw Learn Syst. 2014
May;25(5):934-46. doi: 10.1109/TNNLS.2013.2283730. https://www.ncbi.nlm.nih.gov/pubmed/24808039 developability:
Drug
'developability' assessment has become an increasingly important addition to
traditional drug efficacy and toxicity evaluations, as pharmaceutical scientists
strive to accelerate drug discovery and development processes in a time- and
cost-effective manner. D. Sun et. al, In
vitro testing of drug absorption for drug 'developability' assessment: forming
an interface between in vitro preclinical data and clinical outcome. Curr
Opin Drug Discov Devel.; 7(1): 75- 85, Jan 2004
diagnosis:
Allen
Roses, worldwide director of genetics for Glaxo Wellcome [now Glaxo SmithKline]
notes that “precise diagnoses leading to universal specific treatments are,
for many illnesses, myths... for many diseases there is no accurate, single
diagnostic test” . A.D. Roses “Pharmacogenetics and future drug development
and delivery” Lancet 355 (9212):1358-61 Apr 15, 2000 Narrower
terms: companion diagnostics, molecular diagnostics
directed
evolution:
an iterative process scientists use to design biological molecules like
enzymes. It requires
inducing some randomness in the target enzyme within an organism like
bacteria. The resulting mutated bacteria are screened to see which ones do
the intended job the best. The winners are then cultured, and from their
offspring, the best are selected, and then cultured, and so on.
https://www.vox.com/science-and-health/2018/10/3/17931612/nobel-prize-2018-chemistry-directed-evolution-enzymes-antibodies
diseases:
The
human genome sequence will dramatically alter how we define, prevent, and treat
disease. As more and more genetic variations among individuals are discovered,
there will be a rush to label many of these variations as disease- associated.
We need to define the term disease so that it incorporates our expanding genetic
knowledge, taking into account the possible risks and adverse consequences
associated with certain genetic variations, while acknowledging that a
definition of disease cannot be based solely on one genetic abnormality. Disease
is a fluid concept influenced by societal and cultural attitudes that change
with time and in response to new scientific and medical discoveries.
Historically, doctors defined a disease according to a cluster of symptoms. As
their clinical descriptions became more sophisticated, they started to classify
diseases into separate groups, and from this medical taxonomy came new insights
into disease etiology. K Larissa et. al. "Defining Disease in the Genomics
Era" Science 293 (5531): 807- 808, Aug. 3, 2001 http://www.sciencemag.org/cgi/content/full/293/5531/807 Collections of symptoms
and signs (phenotypes) that appear to be similar … Similar clinical phenotypes
may have very different underlying mechanisms. As genetic capabilities increase,
we will have additional tools to subdivide disease designations that are
clinically identical. Allen D. Roses “Pharmacogenetics and future drug
development and delivery” Lancet 355 (9212):1358- 1361 Apr 15, 2000 disruptive
technologies: Some technologies are improved in a
linear fashion or incrementally. Others truly change the paradigm.
Clayton Christensen writes about these in The Innovator's Dilemma. What
is particularly interesting about Christensen's analysis (based on data from the
disk drive industry) is that he found disruptive technologies tended to be much
cheaper than existing technologies. Existing companies were quite capable of
developing the technologies (and had). What they couldn't do was figure out how
to market them and whether it made sense to devote sufficient resources to them
(which in many cases would not have been the responsible thing to do.) The pharmaceutical
industry is mentioned only in passing, but the success of larger established
companies either partnering with smaller less established ones (clearly
happening in the pharmaceutical and biotechnology sectors) or spin- off of
promising developments as separate companies (Johnson & Johnson said to be
particularly good at this) makes a lot of sense. DNA vaccines:
DNA- mediated immunization, colloquially known as DNA vaccines. This represents
a radical change in the way that antigens are delivered; it involves the direct
introduction of a plasmid DNA encoding an antigenic protein which is then
expressed within cells of the organism. This leads to surprisingly strong immune
responses, involving both the humoral and cellular arms of the immune system.
Robert G. Whelan, DNA Vaccines, Cyberspace and Self Help Programs, Intervirology
39: 120-125 (1996) DNAvaccine. com http://dnavaccine.com/ drug:
Any substance which when absorbed into a living organism
may modify one or more of its functions. The term is generally
accepted for a substance taken for a therapeutic purpose, but is also commonly used for abused substances. Synonymous with medicine, pharmaceutical.
[IUPAC Compendium]
A substance recognized
by an official pharmacopoeia or formulary, a substance intended for use in the
diagnosis, cure, mitigation, treatment, or prevention of disease. A substance
(other than food) intended to affect the structure or any function of the body.
A substance intended for use as a component of a medicine but not a device or a
component, part or accessory of a device. Biologic products are included within
this definition and are generally covered by the same laws and regulations, but
differences exist regarding their manufacturing processes (chemical process vs.
biological process.) CDER, FDA Glossary http://www.fda.gov/cder/drugsatfda/glossary.htm Narrower
terms: specialty pharmaceuticals. Compare biologics.
drug
development costs: Developing a drug is a
risky and hugely expensive undertaking. Some 90% of publicly traded
biopharmaceutical companies are not
expected to make a profit this year, and, profitable or not, such companies
require massive investments in research and development. How massive? The most
thorough study of what it costs to a develop single new drug was conducted by
three PhD economists: Joseph A. DiMasi, director of economic analysis at the Tufts
Center for the Study of Drug Development, Henry G. Grabowski of Duke, and
Ronald W. Hansen of the University of Rochester. Their papers on the subject go
back to 1979 and have been cited by other researchers, including those of the
U.S. government, to analyze policy questions. DiMasi and Grabowski wrote the
chapter, “R&D Costs and Returns to New Drug Development: A Review of the
Evidence,” in The Oxford Handbook of the Economics of the Biopharmaceutical
Industry. Tufts Research, Published in 2016, Examined 106 Drugs at Random The
most recent estimates of the three researchers were published in the May 2016
issue of the Journal
of Health Economics. They looked at the research and development costs of
106 randomly selected drugs from a survey of 10 pharmaceutical firms. These data
were used to estimate the average pre-tax cost of new drug and biologics
development. The costs of compounds abandoned during testing were linked to the
costs of compounds that obtained marketing approval. The researchers determined
that the average out-of-pocket cost per new compound approved by the Food & Drug
Administration was $1.4 billion. http://www.cost-of-health-carenews.com/our-blog/issue-no-21-what-it-costs-to-make-a-pill
drug
discovery: For any given target, HTS High
Throughput Synthesis remains the predominant tool for identifying leads for
further drug development. Those companies that can effectively deal with the
flood of large numbers of potential targets coming out of genomics are those
that can gain a significant competitive advantage. However, this abundance of
new targets is both an opportunity and a threat. When companies are able to
prioritize and validate targets, it allows them to narrow the focus to those
leads offering improved chances of success. Related terms:
target validation
drug
interactions:
Examples of drug interaction terms include adverse drug
interaction, drug- drug interaction, drug- laboratory interaction, drug- food
interaction, etc. Drug interaction is defined as, "An action of a drug on
the effectiveness or toxicity of another drug". .. Due to non- uniform
usage of these terms, it is sometimes difficult to compare various studies and
derive incidence rates, etc. for ADRs, and Drug Interactions Saeed A
Khan, "Drug Interaction or Adverse Drug Reaction? Confusing Terms",
British Medical Journal 10 July, 1998] http://bmj.com/cgi/eletters/316/7149/1930
Drug Safety,
FDA
https://www.fda.gov/news-events/fda-voices-perspectives-fda-leadership-and-experts/new-cder-report-highlights-ongoing-drug-safety-initiatives-and-priorities
Related terms:
idiosyncratic toxicity, pharmacovigilance
drug utilization research:
was defined by WHO in 1977 as «the marketing, distribution,
prescription, and use of drugs in a society, with special emphasis on the
resulting medical, social and economic consequences». Since then, a number of
other terms have come into use and it is important to understand the
interrelationships of the different domains…
Drug
utilization research may also be divided into descriptive and analytical
studies. The emphasis of the former has been to describe patterns of drug
utilization and to identify problems deserving more detailed studies. Analytical
studies try to link data on drug utilization to figures on morbidity, outcome of
treatment and quality of care with the ultimate goal of assessing whether drug
therapy is rational or not. … Drug
utilization research is thus an essential part of pharmacoepidemiology as it
describes the extent, nature and determinants of drug exposure. Over time, the
distinction between these two terms has become less sharp, and they are
sometimes used interchangeably. However, while drug utilization studies often
employ various sources of information that focus on drugs (e.g. aggregate data
from wholesale and prescription registers) the term epidemiology implies defined
populations in which drug use can be expressed in terms of incidence and
prevalence … Drug utilization research also provides insight into
the efficiency of drug use, i.e. whether a certain drug therapy provides value
for money and the results of such research can be used to help to set priorities
for the rational allocation of health care budgets. Introduction to drug
utilization research, WHO World Health Organization 2003
http://apps.who.int/medicinedocs/en/d/Js4876e/2.html
druggable:
Able to be modulated by a small molecule to produce a desired phenotypic change
in cell targets. Variant spelling is drugable, but druggable is more
common. Alternatively/ Related terms: developability, drug-like, drug
likeness, druggable, low hanging fruit, pharmaceutically tractable, privileged
structure efficacy:
Describes the relative intensity with which agonists vary in the
response they produce even when they occupy the same number of receptors and
with the same affinity. Efficacy is not synonymous to intrinsic activity.
The property that enables drugs to produce responses. It is convenient to
differentiate the properties of drugs into two groups, those which cause them to
associate with the receptors (affinity) and those that produce stimulus
(Efficacy). This term is often used to characterize the level of maximal
responses induced by agonists. In fact, not all agonists of a receptor are
capable of inducing identical levels of maximal responses. Maximal response
depends on the efficiency of receptor coupling, i.e., from the cascade of
events, which, from the binding of the drug to the receptor, leads to the
observed biological effect. IUPAC Medicinal Chemistry
electroceuticals: The
first logical step towards electroceuticals is to better map the neural circuits
associated with disease and treatment. This needs to happen on two levels.
On the anatomical level researchers need to map disease-associated nerves and
brain areas and identify the best points for intervention. On the signalling
level, the neural language at these intervention points must be decoded to
develop a "dictionary" of patterns associated with health and disease
states -- a project synergistic with international drives to map the human
brain.
Research
teams across the globe have realised that by targeting individual nerve fibres
or specific brain circuits they may soon be able to treat a wide range of
conditions that have formerly relied on drug-based interventions. This could
include inflammatory diseases such as rheumatoid arthritis, respiratory diseases
such as asthma and diabetes. In the long run you could also control
neuro-psychiatric disorders like Parkinson's and epilepsy. It wouldn't be
possible to treat infectious diseases, since the bacteria and viruses that cause
them aren't directly connected to the nervous system, nor would you be able to
treat cancer directly in this way. However, in both cases you could stimulate
the relevant nerves to boost aspects of the immune system. Electroceuticals
swapping drugs for devices, Wired 28 May 2013 http://www.wired.co.uk/news/archive/2013-05/28/electroceuticals
Related terms: bioelectronics, Genomics: optogenetics enabling
technologies:
Frequently cited
examples of enabling technologies for drug discovery and development are combinatorial
chemistry, high-throughput screening, microarrays, bioinformatics and computational biology,
nanotechnologies, and imaging
(including biosensors and biomarkers). epigenetics: For
years scientists have known that biological fate is not regulated solely by DNA
sequence; super ordinate regulatory mechanisms exist and contribute to determine
the function of genes. Intense research has shown that these mechanisms, broadly
defined as epigenetics, are multifaceted and complex. As researchers continue to
decipher the roles of DNA, RNA, proteins, and environment in inheritance, the
increased understanding of gene regulation and cellular differentiation from
embryogenesis to aging will reveal therapeutic interventions as well as
diagnostic and prognostic tools for disease. evidence- based
toxicology:
Evidence-based
toxicology: a comprehensive framework for causation, Guzelian PS, Victoroff
MS, Halmes NC, James RC, Guzelian CP., Hum Exp Toxicol. 2005 Apr;24(4): 161-201 expression:
The
cellular production of the protein encoded by a particular gene. The
process includes transcription of DNA, processing of the resulting mRNA product
and its translation into an active protein. N.B. A recombinant gene
inserted into a host cell by means of a vector is said to be expressed if the
synthesis of the encoded polypeptide can be demonstrated. IUPAC
Bioinorganic, IUPAC Compendium
A description as to how
a gene demonstrates a phenotype. This can range from production of a mRNA
to a disease. If a disease gene carrier shows signs of the disease gene,
then that gene is expressed. Note that an individual must carry the
disease gene and be penetrant for it before the term expression is
utilized. NHLBI Narrower terms: gene expression, protein
expression. Related terms: expression profiling, molecular profiling
expression
profiling: Expression profiling is driving
the pharmaceutical R&D process. It is being used downstream of target
identification, as a biological readout for target modulation. Targets first
identified through genomics then need to go through validation testing, to see
if a phenotypic change occurs when a target is dysregulated. These targets or
pathways can be modified by using either RNAi, or the use of a chemical ligand
that interacts with a target. The results are compared in order to understand a
compound’s activity for on- and off- target effects.
Refers
to the expression values for a single gene across many experimental conditions,
or for many genes under a single condition. In the terminology of cluster
format, the first case amounts to looking at a row of the data table, and the
second case a column.
fail fast:
Several
high-quality analyses comparing the track record of smaller biotechnology
companies with established pharmaceutical companies have concluded that company
size is not an indicator of success in terms of R&D productivity … the
strongest single correlator with success (odds ratio 3.9) was having a high
termination rate in preclinical/Phase I stages. This indicates that companies
have an early idea of which assets are likely to succeed, and that the companies
most willing to face the hard decisions about which assets to terminate do
better than companies that let assets linger. Does size matter in R&D
productivity? If not, what does? Michael Ringel, Peter Tollman, Greg Hersch and
Ulrik Schulze Nature Reviews Drug Discovery 12:901-902, Dec 2013 http://www.nature.com/nrd/journal/v12/n12/pdf/nrd4164.pdf
Designed
to eliminate high risk compounds at an early stage to free up existing capacity
for more successful compounds. The industry is faced with an increasing number
of unvalidated or poorly validated candidates and targets. Companies risk
decreasing their productivity rate if they end up chasing more low quality drug
candidates. There isn't enough matter in the universe to make all possible
compounds. A term that has tended to make people in drug discovery
and development wince, but considering the costs of later failures, it looks
more and more like an attractive option.
FAIR data Principles : Findable, accessible,
interoperable, reproducible In the eScience ecosystem, the challenge of
enabling optimal use of research data and methods is a complex one with
multiple stakeholders: Researchers wanting to share their data and
interpretations; Professional data publishers offering their services,
software and tool-builders providing data analysis and processing
services; Funding agencies (private and public) increasingly concerned
with proper Data Stewardship; and a Data Science community mining,
integrating and analysing the output to advance discovery. Computational
analysis to discover meaningful patterns in massive, interlinked datasets
is rapidly becoming a routine research activity. Providing
machine-readable data as the main substrate for Knowledge Discovery and
for these eScientific processes to run smoothly and sustainably is one of
the Grand Challenges of eScience.
https://www.force11.org/group/fairgroup/fairprinciples fast track:
The
fast track process was established in the FDA Modernization Act of 1997. Under
this act, NDAs are deemed either "standard" or "priority"
(fast track). With the "standard" designation, the FDA’s goal is to
complete the review and make a decision on the NDA within ten months after it
has been filed. With the "priority" designation, used for drugs that
address unmet medical needs, the target date is six months after the filing.
However, actual approval times are typically longer. In certain cases, the FDA
also offers "accelerated approval" to allow the marketing of drugs for
life-threatening diseases, before the benefits to patients are formally
demonstrated. This approval is made on the basis of a surrogate marker (e.g., a
drug’s effect on survival). FDA US Food
and Drug Administration http://www.fda.gov/default.htm FIPCO Fully Integrated Pharmaceutical Company:
Not as popular a goal in the 21st century as
in the mid-late 1990's.
franchises
- pharmaceutical: In the pharmaceutical industry, we
tend to think of franchises as a suite of relevant drugs marketed to a specific
cluster of physicians. While this definition served our needs for sales
efficiency and scientific credibility, it has left too much value on the table.
We encourage the industry to re-think the idea of franchise in terms of brand
identity, of the images, values and ideas consumers and other stakeholders,
such as pharmacists, associate with a given brand. Vimal Bahuguna and Bob
Lieberman, "From Patents to Franchises, Bogart Delafield Ferrier, US http://www.bdf.com/patentstofranchises.htm function:
The vagueness of the term 'function' when applied to genes or proteins emerged
as a particular problem, as this term is colloquially used to describe
biochemical activities, biological goals and cellular structure. Gene Ontology
Consortium "Gene Ontology: tool for the unification of biology Nature
Genetics 25: 25-29 May 2000 The term
"function" means many things, and its meaning changes depending on who
is asking the question and what sorts of experiments are being employed to probe
it. Genomics by itself cannot usually determine even the biochemical, much less
the cellular or physiological functions of a protein. Structural biology can
determine the shape of the protein but cannot reliably determine its function;
the coupling between overall structure and function is a loose one. Given a
structure, one cannot determine where on the surface of a protein the likely
binding sites for ligands are located and what those ligands are likely to be.
Genomewide experiments have many false positives and false negatives and often
do not distinguish indirect effects from direct ones. The consequences of the
expression of a given gene sequence can only be determined by integrating the
results from many different types of experiments, and the best way to carry out
this integration is not obvious. "From Sequence to Consequence: The Problem
of Determining the Functions of Gene Products in the Age of Genomics" Dr.
Gregory A. Petsko, Brandeis Univ.
Chemogenomics/ Chemical
Genomics Nov. 18- 19, 2002, Boston MA Narrower terms:
gene function, protein function functional
genomics: Functional genomics
aims to discover the biological function of particular genes
and to uncover how sets of genes and their products work together in health and
disease. In its broadest definition, functional genomics encompasses many
traditional molecular genetic and other biological approaches. The development and
application of global (genome- wide or system- wide) experimental approaches to
assess gene function by making use of the information and reagents provided by
structural genomics [in the original more limited sense of construction of high-
resolution genetic, physical and transcript maps of an organism]. It is
characterized by high throughput or large- scale experimental methodologies
combined with statistical and computational analysis of the results. The
fundamental strategy is to expand the scope of biological investigation from
studying single genes or proteins to studying all genes or proteins at once in a
systematic fashion. Phil Hieter and Mark Boguski "Functional Genomics:
It's All How You Read It" Science 278: 601- 602, October 24, 1997 functional proteomics:
Is yielding large
databases of interacting proteins and extensive pathways maps of these
interactions are being scored and deciphered by novel high throughput
technologies. However, traditional methods of screening have not been very
successful in identifying protein- protein interaction inhibitor gene
(cistron): Structurally, a basic unit of hereditary material; an ordered
sequence of nucleotide bases that encodes one polypeptide chain (via mRNA). The
gene includes, however, regions preceding and following the coding region
(leader and trailer) as well as (in eukaryotes) intervening sequences (introns)
between individual coding segments (exons). Functionally, the gene is defined by
the cis- trans test that determines whether independent mutations of the
same phenotype occur within a single gene or in several genes involved in the
same function. IUPAC Compendium There are many
discussions between biologists to find a comprehensive definition of a gene,
which is not easy, if possible at all. For our purposes a gene is a continuous
stretch of a genomic DNA molecule, from which a complex molecular machinery can
read information (encoded as a string of A, T, G, and C) and make a particular
type of a protein or a few different proteins. Alvis Brazma, et. al., A quick
introduction to elements of biology: 3.3 Genes and protein synthesis, European
Bioinformatics Institute, Draft, 2001 http://www.ebi.ac.uk/microarray/biology_intro.html#Genomes
Specific sequences
of nucleotides along a molecule of DNA (or, in the case of some viruses,
RNA) which represent the functional units of heredity. The majority of
eukaryotic genes contain coding regions (codons) that are interrupted by
non- coding regions (introns) and are therefore labeled split genes. MeSH,
1965
A gene
is a DNA segment that contributes to phenotype/ function. In the absence of
demonstrated function a gene may be characterized by sequence, transcription or
homology. Human Gene Nomenclature, HUGO
Genomics
79(4):464-470 (2002) The functional and
physical unit of heredity passed from parent to offspring. Genes are pieces of
DNA, and most genes contain the information for making a specific protein NHGRI This definition doesn't
specify that it applies only to humans - but by specifying "parents"
it seems to rule out non- animal genes, and almost implies mammals, or at least
warm- blooded organisms. gene disruption:
A key methodology in high- throughput gene functional analysis.
Involves developing various methods for systematically disrupting genes throughout the
genome of a model organism (resulting in knockouts, or null mutations
of these genes) and then the phenotype (if any) of the mutant organism.
gene editing:
Gene editing, particularly using the
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas
system, has gained importance both as a research tool in drug discovery
and for drug therapy. Cambridge Healthtech Institute’s fourth annual
symposium on New Frontiers in CRISPR-Based Gene Editing will bring
together experts from research and clinical laboratories to talk about the
recent progress in gene editing and its growing applications. However, the
technology is not without limitations. What is being done to overcome some
of the inherent challenges in guide RNA design, delivery and off-target
effects associated with CRISPR/Cas and what are some of the alternatives
being developed? Experts from pharma/biotech, academic and government
labs, and technology companies will share their experiences leveraging the
utility of CRISPR-based gene editing for creating cell lines and disease
models, for functional in vitro, in vivo and ex vivo screening,
for target and cellular pathway identification, and for therapeutic use.
New Frontiers in CRISPR based Gene Editing 2018 Feb
San Francisco CA
Program
http://www.triconference.com/gene-editing/
|
gene expression:
The process by which a gene’s coded
information is converted into the structures present and operating in the
cell. Expressed genes include those that are transcribed into mRNA and
then translated into protein and those that are transcribed into RNA but not
translated into protein (e.g. transfer [tRNA] and ribosomal [rRNA] RNAs).
[DOE]
The
phenotypic manifestation of a gene or genes by the processes of gene action.
MeSH, 1990
Broader
terms: expression, genome expression Related term: protein expression
gene expression profiling:
The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell.
MeSH, 2000
gene manipulation:
The
use of in vitro techniques to produce DNA molecules containing novel
combinations of genes or altered sequences, and the insertion of these into
vectors that can be used for their incorporation into host organisms or cells in
which they are capable of continued propagation of the modified genes. IUPAC
Biotech gene silencing:
Interruption or suppression of the expression of a gene at transcriptional or
translational levels. MeSH 2000 Narrower term: RNAi RNA interference gene therapy:
Encompasses at least four types of application of genetic engineering for the insertion of genes into humans. The scientific requirements and the ethical issues associated with each type are discussed. Somatic cell gene therapy is technically the simplest and ethically the least controversial. The first clinical trials will probably be undertaken within the next
year [1986]. Germ line gene therapy will require major advances in our present knowledge and it raises ethical issues that are now being debated. In order to provide guidelines for determining when germ line gene therapy would be ethical, the author presents three criteria which should be satisfied prior to the time that a clinical protocol is attempted in humans. Enhancement genetic engineering presents significant, and troubling, ethical concerns. Except where this type of therapy can be justified on the grounds of preventive medicine, enhancement engineering should not be performed. The fourth type, eugenic genetic engineering, is impossible at present and will probably remain so for the foreseeable future, despite the widespread media attention it has received.
W. French Anderson "Human gene therapy: scientific and ethical considerations" J Med Philosophy
10 (3): 275- 291, Aug. 1985
genetic
engineering:
Directed modification of the
gene complement of a living organism by such techniques as altering the DNA,
substituting genetic material by means of a virus, transplanting whole nuclei,
transplanting cell hybrids, etc. MeSH, 1989 Related term:
recombinant DNA technology
genetic
enhancement: The use of genetic methodologies to improve
functional capacities of an organism rather than to treat disease. MeSH,
2002
The subject of much
discussion and concern over the ethics of, though new disease diagnoses,
treatments (and concepts of "disease") are much closer than true
genetic enhancements. The popular conception of selective breeding focuses on
optimization of one or a very few traits (which produces tomatoes which ship
well but have no taste, and purebred dogs with congenital hip dysplasia. Little
attention has been paid to the tradeoffs (predictable and not) inevitable among
polygenic traits.
"Regression to the
mean" also factors in. While two tall or two bright people tend to have
children who are taller or brighter than average, they are NOT usually taller or
brighter than the parents are. Or as George Bernard Shaw said to the actress who
told him they should have children -- "with my looks and your
brain" -- what if it turned out the other way around?
Only microbes with
their greatly enhanced opportunities for evolving (with such short reproductive
spans) seem to quickly get reliably bigger, better (in a sense) and stronger.
Biological homeostasis is incredibly powerful. We may never be able to
"enhance" complex traits such as intelligence or strength. But
we need to learn how to talk about these issues -- preferably before actually
being able to actually implement genetic enhancement.
genetic
testing: Allen Roses, worldwide director of genetics for Glaxo Wellcome [now Glaxo
SmithKline] notes "Until now, government sponsored committees
convened to address ‘genetic testing’ have generally limited their
definition and their reports to concerns regarding diseases caused by single
gene mutations … Another class of 'genetic tests’ is related to
pharmacogenetics, including ... variants or other inherited polymorphic traits
that are not diagnostic of disease … Clear language and differentiation of
respective ethical, legal and societal issues are required to prevent inaccurate
vernacular usage creating a confused public perception. Allen Roses,
Pharmacogenetics and the practice of medicine” Nature 405: 857- 865, 15 June
2000
genome:
The
complete set of chromosomal and extrachromosomal genes of an organism, a cell,
an organelle or a virus; the complete DNA component of an organism. IUPAC
Biotech
The fundamental
concepts of genome, genotype and phenotype are not defined in a
satisfactory manner within the biological literature. Not only are there
inconsistencies in usage between various authors, but even individual authors do
not use these concepts in a consistent manner within their own writings. We have
found at least five different notions of genome, seven of genotype, and five of
phenotype current in the literature. Our goal is to clarify this situation by
(a) defining clearly and precisely the notions of genetic complement, genome, genotype,
phenetic complement, and phenotype; (b) examining that of phenome;
and (c) analysing the logical structure of this family of concepts. M. Mahner,
M. Kary "What exactly are genomes, genotypes and phenotypes? And what about
phenomes?" Journal of Theoretical Biology 186 (1): 55- 63, May 1997 All the DNA contained
in an organism or a cell, which includes both the chromosomes within the nucleus
and the DNA in mitochondria. [NHGRI] Size expressed by the number of base pairs.
[DOE].
First used by H.
Winkler in 1920, was created by elision of the words GENes and chromosOMEs, and
that is what the term signifies: the complete set of chromosomes and their
genes. V McKusick "Genomics: Structural and Functional studies of
genomes" Genomics 45:244-249 Oct. 15 1997
genome editing: Genome editing (also called gene editing) is a group of technologies that
give scientists the ability to change an organism's DNA. These
technologies allow genetic material to be added, removed, or altered at
particular locations in the genome What are genome editing and CRISPR-Cas9? Genetics Home Reference, NIH,
NLM
https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting
genomics:
Generation of information about living things by systematic approaches that can
be performed on an industrial scale. Roger Brent "Genomic biology"
Cell 100: 169-183 Jan 2, 2000
The systematic study of
the complete DNA sequences (GENOME) of organisms. MeSH, 2001 genotype:
The
genetic constitution of an organism as revealed by genetic or molecular
analysis, i.e. the complete set of genes, both dominant and recessive, possessed
by a particular cell or organism. IUPAC Biotech
The observed alleles at a genetic locus for an individual. NHLBI An organism’s genetic
makeup, as revealed through molecular analysis. genotyping:
Used for diagnosis,
drug efficacy, and toxicity. Utilizes genomic DNA that, after digestion, reacts
with a SNP array to obtain an individual SNP pattern. These variations can for
instance provide information about the diagnosis of a certain disease, or the
effectiveness or side effect of a certain drug. May refer to identifying
one or more, up to the entire gene sequence of an organism. Compare phenotype
Genotyping implies (though I haven't found this in print) determining known
variants, as opposed to discovery of new ones.
granularity: Level of detail. As we learn more and more about biology we
find that older concepts are not so much wrong, but that what we knows becomes
more and more granular, and we learn more about what we don't yet know or
understand.
GWAS Genome
Wide Association Sequencing:
An
analysis comparing the allele frequencies of all available (or a whole GENOME
representative set of) polymorphic markers in unrelated patients with a specific
symptom or disease condition, and those of healthy controls to identify markers
associated with a specific disease or condition. MeSH 2009 The NIH is interested
in advancing genome-wide association studies (GWAS) to identify common genetic
factors that influence health and disease. For the purposes of this policy, a
genome-wide association study is defined as any study of genetic variation
across the entire human genome that is designed to identify genetic associations
with observable traits (such as blood pressure or weight), or the presence or
absence of a disease or condition. Whole genome information, when combined with
clinical and other phenotype data, offers the potential for increased
understanding of basic biological processes affecting human health, improvement
in the prediction of disease and patient care, and ultimately the realization of
the promise of personalized medicine. http://grants.nih.gov/grants/gwas/ Pronounced
"gee-wahs"
haplotypes: The genetic constitution of individuals with respect to one member of a pair of
allelic genes, or sets of genes that are closely linked and tend to be inherited
together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. MeSH 1987
haplotyping:
Somatic cells, as opposed to germ cells,
have two copies of each chromosome. A given single- base position may be
homozygous for the wild- type base (each chromosome has the normal allele),
homozygous for a SNP base (each chromosome has the altered allele), or
heterozygous for two different bases (one chromosome has the normal allele and
the other has the abnormal allele). Haplotyping involves grouping subjects
by haplotypes, or particular patterns of sequential SNPs, found on a
single chromosome. These SNPs tend to be inherited together over time and can
serve as disease- gene markers. The examination of single chromosome sets
(haploid sets), as opposed to the usual chromosome pairings (diploid sets), is
important because mutations in one copy of a chromosome pair can be masked by
normal sequences present on the other copy. Genes tend to travel in packs.
This is good news for pharmacogenomics. Broader terms genotyping,
sequencing high-content
screening HTS:
By using multiple
fluorescent reporter systems, combined with high- resolution imaging and high-
throughput image analysis, researchers can observe multiple intracellular events
in individual cells. High- content screening (HCS) enables functional analysis
of target and pathway modulation in living cells by potential drug compounds.
Availability of high- content cellular information at early stages in drug
discovery process will improve the quality of targets, hits, and leads; reduce
late- stage attrition; and shorten time and cost of drug development.
high tech
industry:
The traditional perception of high tech
- still reflected in our indicators - has been research- intensive manufacturing
industries, like computers and aircraft. The penetration of technologies like
information technology, biotechnology, and advanced materials throughout the
economy has, however, changed the basic meaning of high tech. Rather than
referring to the output of R&D intensive industries, high tech now refers to
a style of work applicable to just about every business ... This
change is said to have revolutionized the features of a successful technology
policy. Distributed knowledge, skill, entrepreneurship, together with new forms
of collaboration between firms, universities and the government, can now result
in more effective products and services. Importantly for both firm and
worker income, they can result in significantly differentiated products and
services. In other words, technology policy must be more user- centered and
demand- based than ever before. Nicholas S. Vonortas "US Policy towards
Research Joint Ventures" Nov. 1999 http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.197.5598
high
throughput:
Although the adjective "high throughput"
was originally coined in a drug screening context, high throughput strategies to
accelerate and automate earlier steps in the drug discovery pipeline have
already been introduced. With the introduction of genomics- based drug discovery
strategies, the concept of high throughput has extended to areas like gene
expression analysis, where microarrays allow the simultaneous expression
profiling of thousands of genes in diseased versus normal samples. In the early
stages of disease- gene research, when one wishes to identify alterations in
gene expression that are associated with a disease state with significant
societal impact and potential market value, a microarray- based approach
provides significant acceleration over traditional methods to evaluate candidate
genes one at a time.
high
throughput screening: Process for rapid
assessment of the activity of samples from a combinatorial library or other
compound collection, often by running parallel assays in plates of 96 or more
wells. IUPAC Combinatorial Chemistry
Traditionally describes
the running of a large-scale assay campaign looking at the effects of a large
number of compounds on a biological target. Human Genome Project HGP:
Horace Freeland Judson writes in
"Talking about the genome" (Nature 409:769, 15 Feb. 2001) "The
language we use about genetics and the genome project at times limits and
distorts our own understanding, and the public understanding. Look at the phrase
- or marketing slogan - 'the human-genome project'. In reality, of course we
have not just one human genome but billions. ... Then, too, the entire phrase -
the human- genome project: singular, definite, with a fixed end- point,
completed by 2000, packaged so it could be sold to legislative bodies, to the
people, to venture capitalists. But we knew from the start the genome project
would never be complete.
human
induced pluripotent stem cells hiPS:
Reprogramming
differentiated human cells to induced pluripotent stem (iPS) cells
has applications in basic biology, drug development, and
transplantation. Human iPS cell derivation previously required vectors
that integrate into the genome, which can create mutations and limit
the utility of the cells in both research and clinical applications.
Here, we describe the derivation of human iPS cells using
non-integrating episomal vectors. After removal of the episome, iPS
cells completely free of vector and transgene sequences are derived
that are similar to human embryonic stem (ES) cells in proliferative
and developmental potential.
Junying Yu 1*, Kejin Hu 2, Kim Smuga-Otto 1,
Shulan Tian 3, Ron Stewart 3, Igor I. Slukvin 4,
James A. Thomson 5*
Human Induced Pluripotent Stem Cells Free of Vector and Transgene
Sequences,
Science DOI: 10.1126/science.1172482 published online March 26, 2009 hypercompetitive: In Richard A. D'Aveni's Hypercompetitive Rivalries: Competing
in Highly Dynamic Environments, (1995) he describes
situations in which competitive advantages are not sustainable. Companies
must be willing to cannibalize their own customers and positions, making
all products obsolete including their own. The pharmaceutical industry
is sometimes described as hypercompetitive.
hyphenated
techniques:
Usually involves a combination of
chromatography and/ or mass spectrometry, NMR or other spectroscopy
technologies.
idiosyncratic
toxicity: Few drug development surprises can be as
devastating as toxicity problems that only show up under a combination of
conditions as idiosyncratic toxicity. Because of the role of variations in human
drug metabolizing enzymes there may only be subtle (or no) evidence of such
problems during pre-clinical safety studies. Such problems are also unlikely to
show up in all but the largest clinical trials, but if the side effects are
serious, it can result in product withdrawal.
ill posed
problems:
In the 1960s [Russian mathematician Andrei Nikolaevich] Tikhonov
began to produce an important series of papers on ill- posed problems. He
defined a class of regularisable ill- posed problems and introduced the concept
of a regularising operator which was used in the solution of these problems.
Combining his computing skills with solving problems of this type Tikhonov gave
computer implementations of algorithms to compute the operators which he used in
the solution of these problems.. "Andrei Nikolaevich Tikhonov",
MacTutor History of Mathematics, Univ. of St. Andrews, Scotland, 1999
Problems without a
unique solution, problems without any solution. Life sciences data tends
to be very noisy, leading to ill-posed problems. Interpretation of microarray
and gene expression data is an ill- posed problem. Compare well- posed
problem
immunotherapy: A type of biological therapy that uses substances to stimulate
or suppress the immune system to help the body fight cancer, infection,
and other diseases. Some types of immunotherapy only target certain cells
of the immune system. Others affect the immune system in a general way.
Types of immunotherapy include cytokines, vaccines, bacillus
Calmette-Guerin (BCG), and some monoclonal antibodies. NCI Dictionary of
Cancer terms https://www.cancer.gov/publications/dictionaries/cancer-terms/def/immunotherapy
in
silico:
In a white paper I wrote for the European Commission in 1988 I advocated the
funding of genome programs, and in particular the use of computers. In this
endeavour I coined "in silico" following "in vitro"
and "in vivo" I think that the first public use of the word is
in the following paper: A. Danchin, C. Médigue, O. Gascuel, H. Soldano, A.
Hénaut, From data banks to data bases. Res. Microbiol. (1991) 142: 913-
916. You can find a developed account of this story in my book The
Delphic Boat, Harvard University Press, 2003 personal communication Antoine
Danchin, Institute Pasteur, 2003
Literally "in the
computer". Narrower terms: in
silico biology, in silico modeling, in silico proteomics,
in silico screening, in silico target discovery, virtual cells in
silico Compare in vivo, in vitro
in
vitro diagnostics:
The process of developing a successful in vitro diagnostic (IVD) relies on
the expertise of a diverse group of individuals, including the scientists
who identify the biomarkers of significance, engineers and assay
developers who translate those ideas into a tangible product, and the
sales and marketing staff who get the product into the market. Global and
regional trends have a tremendous effect on the IVD industry. Rising
healthcare costs have led to a greater emphasis on evidence-based medicine
and a focus on improved patient outcomes. An aging population along with
the growing epidemic of chronic diseases and (re)emergence of infectious
diseases are creating a demand for diagnostic devices for a variety of
conditions. The growth of emerging economies and the push for
decentralized healthcare are opening the IVD market to a wider audience.
Healthcare delivery systems are changing, with growing numbers of
integrated delivery networks and accountable care organizations, while
smaller physician and hospital networks are being acquired by larger
corporations and/or are aligning themselves with other small groups.
Commercializing Novel IVDs , Harry Glorikian, Insight Pharma Reports http://www.insightpharmareports.com/Commercializing-Novel-IVDs-Report/\
Executive Summary http://www.insightpharmareports.com/Commercializing-Novel-IVDs-Executive-Summary/ informatics:
The study of the application of computer
and statistical techniques to the management of information. In genome
projects, informatics includes the development of methods to search databases
quickly, to analyse DNA sequence information, and to predict protein
sequence and structure from DNA sequence data. [ORD Office of Rare Diseases,
NIH glossary] information
overload: http://www.genomicglossaries.com/presentation/SLA_outline.asp
information
silos:
The cultural aspects impeding
communication between different groups can be immense, are often not recognized
or articulated, and greatly impede interdisciplinary research. interdisciplinary:
Terminology and ideas relevant to molecular medicine comes from a wide variety
of disciplines: analytical chemistry, artificial intelligence, biochemistry,
bioinformatics, biomechanics, biophysics, biotechnology, cell biology,
clinical and research medicine, computer sciences, developmental and structural
biology, electrochemistry, electronics, engineering, enzymology, epidemiology,
genetic engineering, molecular imaging, immunology, mathematics, microbiology,
molecular biology, optics, pharmacology, public health, statistics, toxicology,
virology and aspects of business, chaos theory, ethics and law are all
relevant. Few people (if any) can be truly interdisciplinary and expert in
all of these subjects. Universities and companies are struggling with the
challenge of (and need to) build bridges between departments and sectors.
We all need to learn more to participate in informed public debate
interoperability:
Ability
of a system or a product to work with other systems or products without special
effort on the part of the customer. Interoperability is made possible by the
implementation of standards. IEEE, Standards Glossary 2010
http://www.ieee.org/education_careers/education/standards/standards_glossary.html
Enabling heterogeneous
databases to function in an integrated way, sometimes refers to cross platform
functionality and operability across relational, object- oriented, and non-
standard types of databases. Related term: FAIR Data "junk DNA":
A general term that encompasses many different types of DNA sequences. These
sequences run the gamut from introns, the parts of genes that are edited out
during protein synthesis; transposable elements, repeated DNA sequences that,
like parasites, duplicate themselves, adding nothing to the genome except more
redundant sequence; and pseudo genes, fossils of one- time genes…all of the
regulatory elements – promoters and inhibitors - required for gene
transcription are spelled out somewhere between the genes. The same is true of
other elements deemed junk, such as introns and RNA genes, which clearly hold
important clues to understanding alternative splicing … the term junk DNA is
frequently used incorrectly. Numerous articles in the medical literature use
junk and non- coding DNA interchangeably. B. Kuska "Bring in Da Noise,
Bring in Da Junk" JNCI 90(15): 1125-1127 Aug. 5, 1998
Dr. Susumu Ohno,
writing in the Brookhaven Symposium on Biology in 1972 in the article
"So Much ‘Junk DNA" in our Genome’ is credited with originating
the term. But his paper was focused "mainly on the fossilized genes, called
pseudo genes, that are strewn like tombstones throughout our DNA. But as the
term caught on in the 1980’s, its meaning was extended to all non- coding
sequences, the vast stretches of DNA that are not genes and do not produce
proteins" (about 95% of the genome) … some [scientists] have begun the
scrap the notion that all non- coding DNA is junk … "I don't think
people take the term very seriously anymore" says Eric Green [NHGRI] whose
group is mapping chromosome 7. B. Kuska "Should Scientists Scrap the Notion
of Junk DNA?" JNCI 90(14): 1032-1033 July 15 1998 Narrower terms
intron, non- coding, repetitive sequences.
knockdowns:
Altering
the function of a gene so that it can be conditionally expressed. This is
necessary when complete knockout of the gene would be lethal to the organism.
| knockins:
Gain of function through addition/ substitution of genetic material. One
example of a knockin is deletion of a coding sequence of a gene in a mouse and
then replacing it with human coding sequences. knockouts:
Inactivation of specific genes. Knockouts are often created in laboratory
organisms such as yeast or mice so that scientists can study the knockout
organism as a model for a particular disease. [NHGRI] Use of particular
techniques to "knock out" the function of a gene in a model organism.
Studying the effects of the gene knockout can help researchers understand the
function of the gene that has been inhibited. Narrower terms:
conditional knockout, random homozygous knockout Related terms gene knockout,
knockdown, knockin, protein knockouts
Laboratory Developed Tests LDTs: A laboratory
developed test (LDT)
is a type of in vitro diagnostic test that
is designed, manufactured and used within a single laboratory.
... For example, sometests can
detect many DNA variations from a single blood sample, which can be used
to help diagnose a genetic disease. FDA, LDTshttps://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/LaboratoryDevelopedTests/default.htm
The Coverage and Analysis Group at the Centers
for Medicare & Medicaid Services (CMS) requested from The Technology
Assessment Program (TAP) at the Agency for Healthcare Research and Quality
(AHRQ) a horizon scan to summarize the available scientific evidence on the
quality of laboratory-developed ("home brew" or "in-house")
molecular tests, which are currently not actively regulated by the U.S. Food and
Drug Administration (FDA). CMS has concerns about the
quality of laboratory-developed tests and the validation currently being
performed on these tests . AHRQ assigned this report to the following Evidence-based Practice Center (EPC):
ECRI EPC (Contract Number: 290 2007 10063 I). To help CMS to address its
concerns, this horizon scan is intended to: 1) identify types of
laboratory-developed molecular tests (LDMTs) currently available for conditions
relevant to the Medicare over-65-year-old population, 2) identify the
methodologies and the processes that have been developed for the assessment of
analytical and clinical performance of molecular tests, 3) summarize the role of
Federal agencies in regulating LDMTs, and 4) identify the quality standards that
have been developed for molecular tests by regulatory bodies, the industry, and
the medical community.
http://www.cms.gov/medicare-coverage-database/details/technology-assessments-details.aspx?TAId=72&bc=BAAgAAAAAAAA&
See also Analyte Specific Reagents lead
optimization: The synthetic modification of a biologically active compound, to fulfill all
stereoelectronic, physicochemical, pharmacokinetic and toxicologic required for
clinical usefulness. IUPAC Medicinal Chemistry
Fueled by the need to
bring down the cost of drug discovery and development, a major shift is
occurring in how pharmaceutical companies evaluate drug leads. Whereas
researchers used to begin by looking at affinity and potency, a
genomics/informatics- based research culture is growing and starting to impinge
on the classical mode. Companies are now concentrating on determining potential
drugs leads' ADMET (absorption, distribution, metabolism, excretion, and
toxicological) properties and manufacturability.
library:
An unordered collection of clones (i.e., cloned DNA from a particular organism),
whose relationship to each other can be established by physical mapping.
[DOE] life cycle
management: Successful drugs follow a typical
pattern of heavy up- front investment in development, followed by market
penetration and peaking sales, followed by a decline in the face of follow- on
drugs or generics. A number of approaches can be used to alter the shape of this
revenue curve, including second- generation follow- on compounds, extended life
through formulation and drug delivery enhancements, outcome studies and
management of the generification process. Some steps can be taken early to
maximize the benefits of drug life cycle management. life
sciences informatics: Informatics are essential at
every step of genomics-based drug discovery and development. The commercial
landscape of life sciences information technology has changed dramatically in
the last few years. Bioinformatics, in particular, has gone through a dramatic
boom/bust. While IT companies are looking to the drug discovery and development
arena as a new market opportunity, pharmaceutical companies are faced with
rising pressure to reduce (or at least control) costs, and have a growing need
for new informatics tools to help manage the influx of data from genomics, and
turn that data into tomorrow's drugs. Key IT tools, such as high- performance
computing, Web services, and grids, are being used to improve the speed and
efficiency of drug discovery and development. True breakthroughs are still
lacking, particularly in key areas such as gene prediction, data mining, protein
structure modeling and prediction, and modeling of complex biological systems.
However, most experts agree that IT and bioinformatics are essential to reaching
the improved productivity the pharmaceutical industry craves. life style
drugs: Drugs
treating conditions such as obesity, erectile
dysfunction, baldness, aging. The attraction is a steady market for which
consumers may well be willing to pay for. low hanging
fruit: The easiest drugs to identify and gain approval for. The big question
these days is how much (if any) "low hanging fruit" is left.
machine learning: At its most simple, machine learning is about teaching computers to learn
in the same way we do, by interpreting data from the world around us,
classifying it and learning from its successes and failures. In fact,
machine learning is a subset, or better, the leading
edge of artificial intelligence. How
did machine learning come about? Building
algorithms capable of doing this, using the binary “yes” and “no” logic of
computers, is the foundation of machine learning – a phrase which was
probably first used during serious research by Arthur Samuel at IBM during
the 1950s. Samuel’s earliest experiments involved teaching machines to
learn to play checkers.
… For
example, in medicine, machine learning is being applied to genomic data to
help doctors understand, and predict, how
cancer spreads,
meaning more effective treatments can be developed. What is Machine
Learning: A complete beginner’s guide in 2017, Bernard Marr, Forbes 2017
May
A type of ARTIFICIAL INTELLIGENCE that enable COMPUTERS to independently
initiate and execute LEARNING when exposed to new data. Year introduced:
MeSH 2016 market forecasting-
pharmaceutical:
Accurately forecasting the market potential for new compounds is becoming an
essential tool in long- term strategic planning, as it aids in various decisions
that are pivotal to the survival and success of a biotech or pharmaceutical
company. Forecasting is used in many situations: to evaluate a licensing
opportunity, to assess a particular lead compound and even in pipeline and
R&D portfolio analyses. Forecasting is also essential in understanding how
the dynamics of a market are changing, and in raising awareness of a company's
current and future competitors. .. Top- down forecasting extrapolates from
available sales data, using algorithms of how a particular drug class or market
has previously performed. Bottom- up forecasting involves reconstructing the
market from its components, which allows the analyst to model how particular
changes over the forecast period will affect the base- year assumptions.
John Earl "What makes a good forecaster?" Nature Reviews Drug
Discovery 2(1): 83, Jan. 2003
http://www.nature.com/drugdisc/nj/articles/nrd1005.html
market fragmentation - pharmaceutical industry:
Currently, the percentage of patients that react favorably to a drug ranges from
20-80%. The market segments itself as patients and doctors switch between
medications in order to find the one that works. In fact, market share may erode
further, even in the absence of significant competition, as physicians avoid
prescribing a drug if a subset of patients suffer toxic side effects. By
defining the population that responds well to a drug, pharmacogenomics can help
secure market share. Blockbusters are still possible if the defined population
is large. mass
spectrometry:
This technique can be used to both
measure and analyze molecules under study. It involves introducing enough energy
into a target molecule to cause its ionization and disintegration. The resulting
fragments are then analyzed, based on the mass/ charge ratio to produce a
"molecular fingerprint."
A significant
technology behind progress in proteomics medical
informatics: The field of information science
concerned with the analysis and dissemination of medical data through the
application of computers to various aspects of health care and medicine. MeSH,
1987 medicinal
chemistry: A chemistry based discipline, also
involving aspects of biological, medical and pharmaceutical sciences. It is
concerned with the invention, discovery, design, identification and preparation
of biologically active compounds, the study of their metabolism, the
interpretation of their mode of action at the molecular level and the
construction of structure- activity relationships IUPAC Medicinal
Chemistry
megabrands:
drugs that post sales of $1 billion in more than 50 countries within two years
of their launch. IMS Reviews Pharma Growth and Outlines Future Trends
ICS Chemical Business 2000 http://www.icis.com/resources/news/2000/03/27/108823/ims-reviews-pharma-growth-and-outlines-future-trends/ Mendelian
genetics: Classical genetics, focuses on monogenic
genes with high penetrance, the tip of the iceberg of genetics. Genomics
is both a narrower and broader term than genetics Metabolic
Engineering ME:
An approach to the understanding and
utilization of metabolic processes. As the name implies, ME is the
targeted and purposeful alteration of metabolic pathways found in an
organism in order to better understand and utilize cellular pathways for
chemical transformation, energy transduction, and supramolecular assembly.
ME typically involves the redirection of cellular activities by the
rearrangement of the enzymatic, transport, and regulatory functions of the
cell through the use of recombinant DNA and other techniques. Much of this
effort has focused on microbial organisms, but important work is being
done in cell cultures derived from plants, insects, and animals. National
Science Foundation, Interagency Opportunities in Metabolic Engineering,
Program Solicitation NSF 05-502, 2004
http://www.nsf.gov/pubs/2005/nsf05502/nsf05502.htm
metabolic
profiling: For investigators of selected
biochemical pathways, it is also often not necessary to view the effects of
perturbation on all branches of metabolism. Instead, the analytical
procedure can be focused on a smaller number of pre- defined metabolites.
Sample preparation and data acquisition can be focused on the chemical
properties of these compounds with the chance to reduce matrix effects. This
process is called
metabolite profiling (or sometimes metabolic profiling). Oliver
Fiehn "Combining genomics, metabolome analysis, and biochemical
modelling to understand metabolic networks" Comparative and Functional
Genomics 2: 155-168, 2001 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447208/ metabolism:
In
case of heterotrophic organisms, the energy evolving from catabolic processes is
made available for use by the organism. IUPAC Medicinal Chemistry
The sum of chemical
changes that occur within the tissues of an organism consisting of anabolism
(BIOSYNTHESIS) and catabolism; the buildup and breakdown of molecules for
utilization by the body. MeSH
The total fate of a
xenobiotic, which includes: absorption, distribution, biotransformation,
metabolism and elimination (ADME). Metabolism and biotransformation are often
used interchangeably, but the latter term does not encompass absorption,
distribution and elimination. Glossary, XenoTech LLC http://xenotechllc.com/Knowledge/Glossary/
Metabolism, Wikipedia,
accessed May 27, 2004 http://en.wikipedia.org/wiki/Metabolism
distinguishes between total metabolism, specific metabolism, cell metabolism
and other types of metabolism.
metabolite:
Any
intermediate or product resulting from metabolism. IUPAC International
Union of Pure and Applied Chemistry, Glossary for Chemists of terms used in
biotechnology. Recommendations, Pure & Applied Chemistry 64 (1): 143-168,
1992 metabolomics:
The study of the metabolite
profiles in biological samples, is growing amidst the current shift toward
translational research. Although there is some debate over what the field should
actually be called, scientists are pushing forward to find uses for metabolomic
profiling, a clinical option that is comparatively cheap and noninvasive.
Charles W. Schmidt, Metabolomics: What's happening downstream of DNA, EHP online
Environmental Health Perspectives, Toxicogenomics, 2004 http://ehp.niehs.nih.gov/txg/members/2004/112-7/focus.html?section=toxicogenomics
The general aim of metabolomics is to
identify, measure and interpret the complex time-related concentration,
activity and flux of endogenous metabolites in cells, tissues, and other
biosamples such as blood, urine, and saliva.
For the purposes of this solicitation, metabolites include small
molecules that are the products and intermediates of metabolism, but also
carbohydrates, peptides, and lipids… It is expected that the technologies
developed under this initiative will play a major role in transferring
capabilities to laboratories and research institutes that are investigating
the underlying pathways involved in cellular homeostasis, perturbation,
development, and aging. Due to pleiotropic
effects, the effect of a single mutation may lead to the alteration of
metabolite levels of seemingly unrelated biochemical pathways. This is
especially liable to happen if genes are constitutively overexpressed or anti-
sense inhibited. A comprehensive and quantitative analysis of all metabolites
could help researchers understand such systems. Since such an analysis
reveals the metabolome of the biological system under study, this approach
should be called metabolomics. Analogous to proteins and
proteomics, metabolomics, or metabonomics, is the study of all the metabolites
of a cell or organism. Identifying and quantifying these components helps to
reveal cellular regulation, pathways, activity, and response under normal and
other conditions. Brush up on your 'omics, Chemical & Engineering News,
81(49): 20, Dec. 2003 http://pubs.acs.org/cen/coverstory/8149/8149genomics1.html
For functional
genomic or plant breeding programmes, as well as for diagnostic usage in
industrial or clinical routines, it might not be necessary to determine the
levels of all metabolites individually. Instead, a rapid classification of
samples according to their origin or their biological relevance might be
more adequate in order to maintain a high through- put. This process can be
called metabolic finger- printing. Such approaches have occasionally been
termed metabonomics, which on the one hand could be mixed up with the
completely different goal of metabolomics, and on the other hand with the
earlier defined concept of the metabolon, the coordinated channelling of
substrates through tightly connected enzyme complexes. Oliver Fiehn,
"Combining genomics, metabolome analysis and biochemical modelling to
understand metabolic networks" Comparative and Functional Genomics
2:155-168 April, 2001 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447208/ metabonome,
metabonomics: The quantitative measurement of the
dynamic multiparametric metabolic response of living systems to
pathophysiological stimuli or genetic modification. This concept has arisen from
work on the application of 1H-NMR spectroscopy to study the
multicomponent measurement of biofluids, cells, and tissues. [J.K. Nicholson,
J.C. Lindon & E. Holmes, "Metabonomics" understanding the
metabolic responses of living systems to pathophysiological stimuli via
multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica
29, 1181-1189, 1999] Total small molecule
complement of a cell. [Jeremy K. Nicholson, J.C. Lindon & E. Holmes.
"Metabonomics": understanding the metabolic responses of living
systems to pathophysiological stimuli via multivariate statistical analysis of
biological NMR spectroscopic data. Xenobiotica
29, 1181-1189, 1999] microarrays:
Tool for studying how large numbers of genes interact with
each other and how a cell’s regulatory networks control vast batteries of
genes simultaneously. Uses a robot to precisely apply tiny droplets containing
functional DNA to glass slides. Researchers then attach fluorescent labels to
DNA from the cell they are studying. The labeled probes are allowed to bind to
cDNA strands on the slides. The slides are put into a scanning microscope to
measure … how much of a specific DNA fragment is present. [NHGRI]
Roger Brent has
compared microarrays to the telescope or microscope because they enable the
observer to see what was previously unobservable. microdosing:
Almost half of new
drugs fail at the transition from animal to human trials. Human microdosing
points the way to smarter drug development and may be the answer to what has
been perceived as a productivity crisis in the industry. By testing only
1% of a pharmacological dose in humans, failures can be identified much earlier
in the development process – at Phase 0. This approach has proven to be
successful in ADME prediction, helping scientists identify which candidates
merit further development. Microdosing technology can also be used to
determine absolute bioavailability, thus aiding drug developers to assess
pharmacodynamics and physiological activity. Gathering scientists together to
discuss this new and important tool certainly seems needed in order to promote
faster, more efficacious drug development. Using microdosing shows promise
of reducing time spent on drugs destined to fail, and also cutting down on the
costs associated with testing. In addition, human microdosing at Phase 0 will
mitigate the need for testing in animals, and can also help to determine the
best animal models to use. Microdosing studies have become possible due in large
part to the technical advances of detection instruments. miniaturization:
Desirable for many technologies for overall cost
reduction (including reduction in the amount of reagents and analytes needed).
Important to remember that building space is often the least available and most
expensive component of a laboratory budget. molecular
diagnostics techniques: MOLECULAR BIOLOGY
techniques used in the diagnosis of disease. Included are such techniques as IN
SITU HYBRIDIZATION of chromosomes for CYTOGENTIC ANALYSIS; OLIGONUCLEOTIDE ARRAY
SEQUENCE ANALYSIS of gene expression patterns in disease states;
identification of pathogenic organisms by analysis of species specific DNA
sequences; and detection of mutations with PCR (POLYMERASE CHAIN
REACTION). MeSH, 2002 molecular
epidemiology:
The application of molecular biology to
the answering of epidemiological questions. The examination of patterns of
changes in DNA to implicate particular carcinogens and the use of molecular
markers to predict which individuals are at highest risk for a disease are
common examples. MeSH, 1994
Looking at epidemiology
from a genetic/genomic and/or biochemical viewpoint. molecular
medicine:
The Journal
of Molecular Medicine publishes
reports describing major advances in the understanding, prevention, diagnosis,
or treatment of human disease through the application of molecular biology and
gene technology, a research discipline that has become known as molecular
medicine.. Journal of Molecular Medicine, Springer, Aims and Scope http://www.springer.com/biomed/molecular/journal/109
Alternatively/related
terms: clinical genomics, predictive medicine
molecular
modeling, molecular modelling: A technique for the
investigation of molecular structures and properties using computational
chemistry and graphical visualization techniques in order to provide a plausible
three- dimensional representation under a given set of circumstances.
IUPAC Medicinal Chemistry, IUPAC Computational molecular
pathology: What is new in
"molecular pathology" is the emphasis on assessing gene expression
in addition to morphology, and the use of gene expression analysis to validate
large numbers of targets. (However, histochemistry and immunohistochemistry
have been used, for specific proteins, since before the advent of genomics.)
Corporate genomic researchers are increasingly seeking access to human tissue
samples via collaborations with pathology departments at clinical research
institutions. monoclonal
antibodies: A single species of immunoglobulin
molecules produced by culturing a single clone of a hybridoma cell. MAbs
recognize only one chemical structure, i.e., they are directed against a single
epitope of the antigenic substance used to raise the antibody. IUPAC Biotech Antibodies produced by
clones of cells such as those isolated after hybridization of activated B
lymphocytes with neoplastic cells. These hybrids are often referred to as
hybridomas. MeSH, 1982 multibusters:
Multiple drugs for a single indication, efficacious in identifiable sub-
populations. Related term: blockbuster drugs multiplex:
A sequencing approach that uses several pooled samples, greatly increasing
sequencing speed. DOE Simultaneous
amplification of multiple gene products within the same reaction. Chamberlain,
J.S. et al. Nucleic Acids Research 16, 11141, 1988 In general, primer-
extension technologies are amenable to high- throughput applications and
automation, yet only very low levels of multiplexing are possible. Higher
multiplexing can be accomplished by combining primer- extension technology with
microarray technology.
Originally a math term
meaning multiple, later a 19th century telecommunications term,
dating from the telegraph. Oxford English Dictionary nanomedicine:
The monitoring, repair, construction and control of human biological systems at
the molecular level, using engineered nanodevices and nanostructures. [Robert A.
Freitas, Nanomedicine, Foresight Institute, 1998- 2002] http://www.foresight.org/Nanomedicine/ Obtaining thorough,
reliable measures of quantity is the vital first step of nanomedicine. …
Research conducted over the first few years will be spent gathering extensive
information about how molecular machines are built. A key activity during this
time will be the development of a new kind of vocabulary —lexicon — to
define biological parts and processes in engineering terms. …Once researchers
have completely catalogued the interactions between and within molecules, they
can begin to look for patterns and a higher order of connectedness than is
possible to identify with current experimental methods. Mapping these networks
and understanding how they change over time will be a crucial step toward
helping scientists understand nature’s rules of biological design.
Understanding these rules will, in many years’ time, enable researchers to use
this information to address biological issues in unhealthy cells. The
availability of innovative, body-friendly nanotools will help scientists figure
out how to build synthetic biological devices, such as miniature, implantable
pumps for drug delivery or tiny sensors to scan for the presence of infectious
agents or metabolic imbalances that could spell trouble for the body. NHGRI,
Nanomedicine, 2007 http://www.genome.gov/11508736 The goal of the Common
Fund's Nanomedicine program is to determine how cellular
machines operate at the nanoscale level and then use these design principles to
develop and engineer new technologies and devices for repairing tissue or
preventing and curing disease. Nanomedicine, NIH Common
Fund
http://commonfund.nih.gov/nanomedicine/ Nanomedicine
Taxonomy
www.ifm.liu.se/physchem/courses/NKEC18/Nanomedicinetaxonomy.pdf
nanoscience:
The study of phenomena and manipulation of materials at atomic,
molecular and macromolecular scales, where properties differ significantly from
those at a larger scale. Draft definitions, Royal Society, Royal Academy of
Engineering Nanotechnology and Nanoscience, 2003 http://www.nanotec.org.uk/draftdefinition.htm NCE New
Chemical Entity A compound not previously described
in the literature. IUPAC Medicinal Chemistry
Compare:
me too drug NDA New Drug
Application: For
decades, the regulation and control of new drugs in the United States has been
based on the New Drug Application (NDA). Since 1938, every new drug has been the
subject of an approved NDA before U.S. commercialization. The NDA
application is the vehicle through which drug sponsors formally propose that the
FDA approve a new pharmaceutical for sale and marketing in the U.S. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/NewDrugApplicationNDA/ networks:
Although there is no consensus definition of "program" or
"networks", these terms are most often encountered and understood in
the context of the regulatory interactions that link groups of genes and gene
products in developmental processes. Many of these linkages have recently
been elucidated in considerable detail for key events in a variety of species.
Sean Carroll "Communications breakdown?" (book review) Science 291:
1264-1265, Feb. 16, 2001 There are three
bottlenecks in the numerical analysis of biochemical reaction networks. The
first is the multiple time scales involved. Since the time between biochemical
reactions decreases exponentially with the total probability of a reaction per
unit time, the number of computational steps to simulate a unit of biological
time increases roughly exponentially as reactions are added to the system or
rate constants are increased. The second bottleneck derives from the necessity
to collect sufficient statistics from many runs of the Monte- Carlo simulation
to predict the phenomenon of interest. The third bottleneck is a practical one
of model building and testing: hypothesis exploration, sensitivity analyses, and
back calculations, will also be computationally intensive. [Lawrence Berkeley
Lab "Advanced Computational Structural Genomics" Glossary] Narrower
terms: biochemical networks, molecular networks. Related terms: network
models, pathways
new paradigms:
An investigation by Science revealed that use of the term "new
paradigm" in MEDLINE and the ISI database of leading journals increased
steadily during the 1990’s, as did its use in NIH and NSF databases of new
grants. J Cohen "The March of Paradigms" Science 283 : 1998-1999 Mar
26, 1999
While many
advances are unlikely to be truly new paradigms, a few developments show signs
of being more than incremental improvements. Roger Brent compares microarrays to
the microscope and telescope because they "enable observation of the
previous unobservable" [transcripts expressed under different conditions in
cells, tissues, and organisms] [R. Brent, "Functional genomics: learning to
think about gene expression data" Current Biology 9: R338-R341, May 1999]
This is no overstatement.
next
generation sequencing:
Next-generation sequencing (NGS) has taken the worldwide biomedical
research community by storm. Funding is relatively abundant for the moment,
collaborative programs and consortia abound, and early results in many cases
appear to justify all the activity. Many observers sense imminent new
revelations and even paradigm shifts offering significant improvements in the
understanding and treatment of disease. Insight Pharma Reports Next-Generation
Sequencing Technologies: Applications and Markets 2010
NME New
Molecular Entity:
A
New Molecular Entity is an active ingredient that has never before been marketed
in the United States in any form.
FDA, Glossary Drugs@FDA, 2012, http://www.fda.gov/cder/drugsatfda/glossary.htm
NMR Nuclear
Magnetic Resonance: A technology for protein
structure determination. NMR generally gives a lower- resolution structure
than X-ray crystallography does, but it does not require crystallization. . nonlinear:
Advances
in biopharmaceutical technologies are a mix of incremental improvements to
existing technologies (linear) and occasionally, a truly new paradigm or
breakthrough. nutraceuticals:
Foods
with specific health or medical benefits. Differentiate from supplements, which
supplies missing nutrients. Examples include folic acid (to prevent birth
defects) or pectin (to lower cholesterol) and fiber (to reduce the risk of color
cancer). Sometimes spelled nutriceutical. off label:
The
use of an FDA- approved drug or device for a purpose other than that intended by
the manufacturer and described on the label. FDA only approves drugs or devices
for their intended use as described on the label. Neal Holtzman, Michael Watson
"Promoting Safe and Effective Genetic Testing in the United States: Final
Report" glossary, 1997 http://www.nhgri.nih.gov/ELSI/TFGT_final/glossary.html -omes:
A key approach in genomic research is to divide the cellular contents into
distinct sub- population, each given an -omic term. Broadly, these 'omes can be
divided into those that represent a population of molecules, and those that
define their actions. ... Once the individual sub- populations are defined and
analyzed, we can then try to reconstruct the full organism by interrelating
them, eventually allowing for a full and dynamic view of the cell. ... A problem
in comparing the different 'omes' is that each represents a different set of
genes. Mark Gerstein "What is Bioinformatics?" Molecular Biology &
Biochemistry 474b3, Yale Univ. 2001 http://bioinfo.mbb.yale.edu/what-is-it.html In physics, probably
starting with Faraday's ion, cation, anion, the -on suffix has tended to
signify an elementary particle, later materially focused on the photon,
electron, proton, meson, etc., whereas -ome in biology has the opposite
intellectual function, of directing attention to a holistic abstraction, an
eventual goal, of which only a few parts may be initially at hand. Joshua
Lederberg and Alexa T. McCray "'Ome Sweet 'Omics: A Genealogical Treasury
of Words" Scientist 15 (7): 8 April 2, 2001
According to the Oxford
English Dictionary this is an Anglicized version of the suffix
"oma", primarily found in botanical terms and usually meaning
normal, in contrast to the pathology implied by "oma". ontologies:
What is an ontology?, W3C, Requirements for a web ontology language, [work in
progress] http://www.w3.org/TR/webont-req/#onto-def
optogenetics: A
rapidly evolving field of technology that allows optical control of genetically
targeted biological systems at high temporal and spatial resolution. By
heterologous expression of light-sensitive microbial membrane proteins, opsins,
cell type-specific depolarization or silencing can be optically induced on a
millisecond time scale. …
Although recent developments in optogenetics have largely focused on
neuroscience it has lately been extended to other targets, including stem cell
research and regenerative medicine. The
optogenetic (r)evolution, Martin L Rein, Jan M. Deussing, Mol
Genet Genomics. 2012 February; 287(2): 95–109, Published online 2011
December 20. doi: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266495/ organization
of pharmaceutical R&D: By far the most common
organizational structure within pharmaceutical R&D is based on therapeutic
indications. As target pathways and target families become better recognized as
opportunities for synergistic development that cut across disease indications,
what are the implications for how best to capture this synergy? As molecular
tools are increasingly applied beyond target biology to more of the entire
development process, how can expertise in specific tools best be leveraged
across different departments? As chemistry and biology become more intertwined,
how can researchers trained in one discipline or the other learn to better
communicate with each other? As researchers trained in reductionist techniques
and used to working on small projects become involved in much larger systems
biology and high throughput chemistry projects, how does this change the nature
of the work they do? What organizational structures and policies may facilitate
optimal performance under these changing conditions? I have hoped drug
companies which encouraged open sharing of scientific information would prosper
in the long run, without finding much evidence (even anecdotal) until I read
this report, which quantified the positive correlation between companies
encouraging peer reviewed scientific publication and productivity (patents
issued to company scientists and articles published in peer- reviewed journals
by company scientists). Diffusion of Science Driven Drug Discovery
Organizational Change in Pharmaceutical Research, Iain M. Cockburn,
Rebecca Henderson and Scott Stern, NBER, Sept. 1999 http://www.cid.harvard.edu/cidbiotech/events/henderson.htm orphan drugs:
The Orphan
Drug Designation program provides
orphan status to drugs and biologics which are defined as those intended for the
safe and effective treatment, diagnosis or prevention of rare diseases/disorders
that affect fewer than 200,000 people in the U.S., or that affect more than
200,000 persons but are not expected to recover the costs of developing and
marketing a treatment drug. FDA
https://www.fda.gov/forindustry/developingproductsforrarediseasesconditions/default.htm
may be defined as Drugs
that are not developed by the pharmaceutical industry for economic reasons
but which respond to public health need. Actually, the
indications of a drug may also be considered as ' orphan ' since a
substance may be used in the treatment of a frequent disease but may not
have been developed for another, more rare indication. In
fact, three cases may arise : Products
intended to treat rare diseases : These products are developed to treat
patients suffering from very serious diseases for which no treatment, or
at least a satisfactory one, has so far been available. These diseases
affect only a small proportion of the population (less than one person per
2,000 in Europe), most often at birth or in infancy. The number of rare
diseases for which no treatment is currently available is estimated to be
between 4,000 and 5,000 world-wide. Twenty-five to 30 million people are
reported to be affected by these diseases in Europe. Products withdrawn
from the market for economic or therapeutic reasons : For example,
thalidomide widely much used as a hypnotic drug some years ago and was
then withdrawn from the market when its high teratogenic (triggering fetal
malformations) risk was discovered. However this drug showed very
interesting analgesic proprieties in diseases such as leprosy or lupus
erythematosus. They are diseases for which no satisfactory treatment has
been available. Products that have not been developed :either because they
are derived from a research process that cannot be patented ; or because
they concern important markets which are, however, not creditworthy (see
the text Orphan
drugs for Third-World countries). Orphanet About orphan drugs https://www.orpha.net/consor/cgi-bin/Education_AboutOrphanDrugs.php?lng=EN orphan genes:
Putative
ORFs without any resemblance to previously determined protein- coding sequences…While
theoretical evolutionary arguments support the reality of genes when homologues
are found in a variety of distant species, this is not the case for orphan genes
… Our results suggest that a vast majority of E. coli
ORFs presently annotated as “hypothetical” correspond to bona fide genes. J
Alimi et al “RT-PCR validation of 25 “orphan” genes” Genome Research
2000 Jul; 10 (7): 959- 966 Related terms: deorphaning,
deorphanizing, orphan proteins orphan
products: The
Orphan Drug Act (ODA) provides
for granting special status to a product /indication combination upon request of
a sponsor, and if the product/indication combination meets certain criteria.
This status is referred to as orphan designation. Orphan designation qualifies
the sponsor of the product for the tax credit and marketing exclusivity
incentives of the ODA. [FDA, US Orphan Product Designation, 2001] http://www.fda.gov/orphan/designat/index.htm outcomes
research: The terms "outcomes research"
and "effectiveness research" have been used to refer to a wide range
of studies, and there is no single definition for either that has gained
widespread acceptance. As these fields evolved, it appears that "outcomes
research" emerged from a new emphasis on measuring a greater variety of
impacts on patients and patient care (function, quality of life, satisfaction,
readmissions, costs, etc). The term "effectiveness research" was used
to emphasize the contrast with efficacy studies, and highlighted the goal of
learning how medical interventions affected real patients in "typical"
practice settings (OTA,
1994). Effectiveness studies sought to understand the impact of health care
on patients with diverse characteristics, rather than highly homogeneous study
populations. While the terms may have different initial roots, there does not
appear to be much value in distinguishing these activities, and the field is
generally referred to as OER. .. OER evaluates the impact of health care
(including discrete interventions such as particular drugs, medical devices, and
procedures as well as broader programmatic or system interventions) on the
health outcomes of patients and populations. OER may include evaluation of
economic impacts linked to health outcomes, such as cost- effectiveness and cost
utility. OER emphasizes health problem- (or disease-) oriented evaluations of
care delivered in general, real- world settings; multidisciplinary teams; and a
wide range of outcomes, including mortality, morbidity, functional status,
mental well- being, and other aspects of health-related quality of life.
[Outcome of Outcomes Research at AHCPR: Final Report, Agency for Health Care
Policy and Research, AHCPR Publication No. 99-R044] http://www.ahrq.gov/clinic/out2res/outcom1.htm
PAINS
Pan Assay Interference Compounds: A
true drug inhibits or activates a protein by fitting into a binding site on the
protein. Artefacts have subversive reactivity that masquerades as
drug-like binding and yields false signals across a variety of assays.
These molecules. have defined structures, covering several classes of compounds.
… But biologists and inexperienced chemists rarely recognize them. .. Time and
research money are consequently wasted in attempts to optimize the activity of
these compounds. Chemical con artists foil drug discovery, Jonathan Baell,
Michael A. Walters, Nature 513: 481-483, 25 Sept 2014 doi:
10.1038/513481a https://www.nature.com/news/chemistry-chemical-con-artists-foil-drug-discovery-1.15991
patent
cliff: A
colloquialism to denote the potential sharp decline in revenues upon patent
expiry of one or more leading products of a firm. http://www.investopedia.com/terms/p/patent-cliff.asp#ixzz2Esh3BTKi
“Investors
are increasingly willing to accept that pharma companies can navigate the patent
cliff through factors including growth in emerging markets, cost management,
diversification and in some cases new drug launches,” said Deutsche Bank
analyst Mark Clark “ Big
pharma approaching bottom of patent cliff,, Nature Blog Oct 2012 http://blogs.nature.com/news/2012/10/big-pharma-approaching-bottom-of-patent-cliff.html patent
pooling: A patent pool is an agreement between two or more patent owners to license one
or more of their patents to one another or third parties. A patent pool
allows interested parties to gather all the necessary tools to practice a
certain technology in one place, e.g, "one- stop shopping," rather
than obtaining licenses from each patent owner individually. US Patent and
Trademark Office "USPTO issues white paper on patent pooling" Jan.
19, 2001 http://www.uspto.gov/web/offices/com/speeches/01-06.htm patent
stacking: Taking out many patents
for different aspects of a single innovation, thus forcing several royalty
applications and payments. Aaron Cosbey , Sustainable Development Effects of the
WTO TRIPS Agreement: A Focus on Developing Countries, International Institute
for Sustainable Development, Canada, 2000 http://www.iisd.org/trade/trips.htm#_Toc364270391 patent
thickets:
An overlapping set of patent rights requiring those seeking to commercialize new
technology obtain licensees from multiple patentees. Navigating the patent
thicket, Carl Shapiro, Univ. of California, Berkeley, Mar. 2001 http://faculty.haas.berkeley.edu/shapiro/thicket.pdf pathways:
A general term meant to include all forms of molecular transactions and
processes that are part of biochemical systems. Some of these pathways may
involve linear processing, but many involve complex branches, convergences, and
even cycles. .... There are several different classes of biochemical pathways:
metabolic pathways, signal transduction cascades, genetic networks, and drug
metabolism pathways. In addition, protein interaction data links protein
data objects, and can therefore also be conceptualized as graphs. Although the
relationship of protein- interaction maps with biochemical pathways is
undeniable, it is not obvious. ... the design of adequate models for bio-
process representation, manipulation and simulation is still a very open field
of research. In conclusion, we will need to examine and discuss the
relationships between all pathway information, protein interaction data, and
biological process information in order to successfully produce informatics
specifications for any of these kinds of data. Biopathways
Consortium "Definition" http://www.biopathways.org/
Pathway elucidation is critical, in order to both identify the biochemical
components in a pathway associated with disease, and the affect of a chemical
entity on this pathway. This synergistic approach will help to identify ways to
validate and prioritize targets, and enable us to understand the molecular
mechanism of therapeutics. The term biochemical
pathways has principally referred to metabolic pathways, which are the
pathways by which a cell converts compounds that enter it into cellular
components (e.g., small molecules and macromolecules including proteins, nucleic
acids, storage carbohydrates, and fatty acids) and by which the cell derives
energy. Signaling pathways are biochemical pathways that regulate cellular
characteristics and processes such as physiology, proliferation, changes in
shape and motility, differentiation, adhesion, and intercellular interactions.
High- content screening approaches can be used to help elucidate pathways.
PCR Polymerase
Chain Reaction:
A laboratory technique to rapidly amplify pre-
determined regions of double- stranded DNA. Generally involves the use of a heat
stranded DNA polymerase. IUPAC Bioinorganic
In vitro
method
for producing large amounts of specific DNA or RNA fragments of defined length
and sequence from small amounts of short oligonucleotide flanking sequences (primers).
The essential steps include thermal denaturation of the double- stranded target molecules, annealing of the primers to their complementary sequences, and
extension of the annealed primers by enzymatic synthesis with DNA polymerase.
The reaction is efficient, specific, and extremely sensitive. Uses for the
reaction include disease diagnosis, detection of difficult to isolate pathogens,
mutation analysis, genetic testing, DNA sequencing, and
analyzing evolutionary relationships. [MeSH, 1991]
Originally
described in 1984 by Kary B. Mullis, who shared the Nobel Prize for Chemistry
for this invention in 1993, PCR enables the amplification of specific nucleotide
sequences through the use of a DNA polymerase. The sequence to be amplified is
identified through the use of synthetic oligonucleotides that are complementary
to the two terminal regions of the targeted sequence.
personalized
medicine: The ability to offer the appropriate
treatment to the right person, only when needed. PGx: may
be pharmacogenomics or pharmacogenetics.
pharmacoepidemiology:
applies
epidemiological methods to studies of the clinical use of drugs in populations.
A modern definition of pharmacoepidemiology is: «the study of the use and
effects/side-effects of drugs in large numbers of people with the purpose of
supporting the rational and cost-effective use of drugs in the population
thereby improving health outcomes… Pharmacoepidemiology may be drug-oriented,
emphasizing the safety and effectiveness of individual drugs or groups of drugs,
or utilization-oriented aiming to improve the quality of drug therapy through
pedagogic (educational) …
Sophisticated utilization-oriented pharmacoepidemiology may focus on the drug
(e.g. dose-effect and concentration-effect relationships), the prescriber (e.g.
quality indices of the prescription), or the patient (e.g. selection of drug and
dose, and comparisons of kidney function, drug metabolic phenotype/genotype,
age, etc.). intervention. …
The initial focus of pharmacoepidemiology was on the safety of individual drug
products (pharmacosurveillance), but it now also includes studies of their
beneficial effects. … Pharmacoepidemiological studies often make useful
contributions to our knowledge about effectiveness and safety, because, unlike
clinical trials, they assess drug effects in large, heterogeneous populations of
patients over longer periods. Introduction
to drug utilization research, WHO World Health Organization 2003
http://apps.who.int/medicinedocs/en/d/Js4876e/2.html pharmacogenetics:
The study of existing genetic knowledge, and the generation of new genetic
data, to understand and thus avoid DRUG TOXICITY and adverse effects from toxic
substances from the environment. MeSH 2004
Pharmacogenetics and pharmacogenomics are frequently interchanged terms
and can therefore be confused. For the purpose of clarity in the use of
the terms in this review, pharmacogenetics is defined as the study of
variability in drug responses attributed to hereditary factors in
different populations. Pharmacogenomics is the determination and analysis
of the genome (DNA) and its products (RNA and proteins) as they relate to
drug response. For example, gene expression profiling using various
microarray technologies has enabled the demonstration of distinct sub-sets
of genes that may be expressed differentially in disease and healthy
tissues. These genomic techniques can be useful for differential diagnosis
of patients, particularly for heterogeneous diseases that present with
similar clinical phenotypes but differ in molecular expression. Response
to treatment can sometimes be recognized at the genomic level by tissue
gene expression profiles. Expression profiles, however, differ from the
approach of using inherited differences in our genetic information to
predict responses to medicines, pharmacogenetics.
Allen D. Roses; Pharmacogenetics, Human
Molecular Genetics,
Volume 10, Issue 20, 1 October 2001, Pages 2261–2267, https://doi.org/10.1093/hmg/10.20.2261
https://academic.oup.com/hmg/article/10/20/2261/559355
A subset of
pharmacogenomics encompassing the study of genetic variation underlying
differential response to drugs, particularly genes involved in drug
metabolism. With the implementation of pharmacogenetics, diseases
will be evaluated by mechanisms, rather than just symptoms, and early response
will be based on prognosis and susceptibility rather than just diagnosis. It
will introduce a bottom- up approach to disease, which will be defined in terms
of its heterogeneity, and not "averaged out" to conform to a uniform
model. pharmacogenomics:
Comprises the study of variations in targets or target pathways, variation in
metabolizing enzymes (pharmacogenetics) or, in the case of infectious organisms,
genetic variations in the pathogen. CHI Drug Discovery Map
http://www.healthtech.com/drugdiscoverymap.asp Pharmacogenomics is the
analysis of the effect of genomics — in particular, genetic variation
(polymorphisms) — on drug response. This practice can potentially help
clinicians administer more tailored treatment. The term pharmacogenetics
is often used to refer specifically to tests that predict drug response;
however, the terms pharmacogenetics and pharmacogenomics are
often used interchangeably.
Can be construed as the
study of the entire complement of pharmacologically relevant genes, how they
manifest their variations, how these variations interact to produce phenotypes,
and how these phenotypes affect drug response. A key element of pharmacogenomics
is, not surprisingly, the large- scale and high throughput collection of data,
including DNA sequence variations, mRNA expression analysis, enzyme kinetic
assays, and cellular localization experiments. Russ Altman "Challenges for
Biomedical Informatics and Pharmacogenomics, Annual Review of Pharmacology &
Toxicology 2002
https://www.annualreviews.org/doi/abs/10.1146/annurev.pharmtox.42.082401.140850?journalCode=pharmtox
The study of how an
individual's genetic inheritance affects the body's response to drugs and holds
the promise that drugs might one day be tailor- made for individuals and adapted
to each person's own genetic makeup. Environment, diet, age, lifestyle, and
state of health all can influence a person's response to medicines, but
understanding an individual's genetic makeup is thought to be the key to
creating personalized drugs with greater efficacy and safety.
Pharmacogenomics combines traditional pharmaceutical sciences such as
biochemistry with annotated knowledge of genes, proteins, and single nucleotide
polymorphisms. Human Genome Project Information, Pharmacogenomics, Oak Ride
National Lab, 2001
From pharmacology
+ genomics. Alternatively:
individualized medicine, personalized medicine, pharmacoproteomics pharmacovigilance:
The aims of pharmacovigilance are to enhance patient care and patient safety in
relation to the use of medicines, especially with regard to the prevention of
unintended harm from the use of drugs; to improve public health and safety in
relation to the use of medicines by the provision of reliable, balanced
information resulting in more rational use of drugs; and to contribute to the
assessment of the risk-benefit profile of medicines, thus encouraging safer and
more effective use of medicines and a resolution of the sometimes
apparently conflicting interests of public health and individual patient
welfare. WHO 2006 http://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/index.html The process of (a)
monitoring medicines as used in everyday practice to identify previously
unrecognised or changes in the patterns of their adverse effects; (b) assessing
the risks and benefits of medicines in order to determine what action, if any,
is necessary to improve their safe use; (c) providing information to users to
optimise safe and effective use of medicines; (d) monitoring the impact of any
action taken. Medicines Control Agency, UK, Pilot publication scheme, Glossary
of terms, 2003 http://www.mca.gov.uk/pilot/app1.htm#A
Related
terms: Phase IV/postmarketing surveillance pharming:
Use
of transgenic animals to produce drugs in their milk, urine or
eggs. Transgenic plants can also be used. (Tobacco is said to be
particularly amenable to this application). Phase IV/
postmarketing surveillance: At this
stage, after a drug has been launched, pharmaceutical companies may conduct
further studies of its performance, often examining long- term safety.
Phase
zero, Phase O:
Phase 0 studies are exploratory studies that often
use only a few small doses of a new drug in a few patients. They might test
whether the drug reaches the tumor, how the drug acts in the human body, and how
cancer cells in the human body respond to the drug. The patients in these
studies might need extra tests such as biopsies, scans, and blood samples as
part of the study process.The biggest difference between phase 0 and the later
phases of clinical trials is that there’s almost no chance the volunteer will
benefit by taking part in a phase 0 trial – the benefit will be for other people
in the future. Because drug doses are low, there’s also less risk to the patient
in phase 0 studies compared to phase I studies. Phase 0 studies help researchers
find out whether the drugs do what they’re expected to do. If there are problems
with the way the drug is absorbed or acts in the body, this should become clear
very quickly in a phase 0 clinical trial. This process may help avoid the delay
and expense of finding out years later in phase II or even phase III clinical
trials that the drug doesn’t act as expected to based on lab studies. Phase 0
studies aren’t used widely, and there are some drugs for which they wouldn’t be
helpful. Phase 0 studies are very small, often with fewer than 15 people, and
the drug is given only for a short time. They’re not a required part of testing
a new drug. American Cancer Society, Phase Zero Clinical trials https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/what-you-need-to-know/phases-of-clinical-trials.html Related terms: microdosing
phenotypic
screens: look
at the effects, or phenotypes, that compounds induce in cells, tissues or whole
organisms … Beginning in the 1980s, advances in molecular biology and genomics
led to phenotypic screens largely being replaced by screens against defined
targets implicated in disease.… some researchers have concluded that
reductionist approaches such as target-based screening are useful but may also
limit the breadth of new findings. Phenotypic
screening, take two Kotz,
J.SciBX 5(15); doi:10.1038/scibx.2012.380 Published online April 12
2012
http://www.nature.com/nrd/journal/v13/n8/full/nrd4366.html
Compare
targeted based drug discovery, screens pipelines:
The process of drug development has evolved into an extremely complex procedure.
The average drug takes 12 years and $270 million from initial discovery to
public usage.(1) For every drug that is deemed marketable by the FDA, thousands
of others are considered either unsafe or ineffective clinically. Beginning with
preclinical research, new chemical entities (NCEs) are discovered in
laboratories and tested in animals for safety and biological activity. If a
compound is thought to be safe and effective as a chemical agent, a
pharmaceutical company then submits an investigational new drug application
(NDA) to the FDA. Once approved for clinical studies, a three-phase process
begins where safety and efficacy are continually assessed with increased
scrutiny and an increasing patient population. Approximately 70% of drugs
entering clinical trials complete Phase I, 33% complete Phase II, and 27%
complete Phase III. After Phase III is completed a company then submits a NDA to
the FDA. Those drugs that are approved for marketing comprise an extremely small
percentage of new chemical entities (NCEs) that are tested. In fact, from
thousands only a handful of drugs undergo clinical studies, and even fewer
receive market approval. C. Daniel Mullins et. al. " Projections of drug
approvals, patent expirations and generic entry from 2000 to 2004" report
prepared for the Dept. of Health and Human Services' Conference on
Pharmaceutical Pricing Practices, Utilization and Costs August 8- 9, 2000,
Washington DC, US http://aspe.hhs.gov/health/reports/Drug-papers/Mullins-Palumbo%20paper-final.htm portfolio
management: For many pharmaceutical companies,
much of the focus in managing portfolio risk has focused on R&D choices for
pipeline products, as well as research portfolio choices on the drug discovery
side. In addition to these levers, there is significant opportunity for
pharmaceutical companies to manage risk through smarter investment in life-
cycle management. These investments span a variety of functions from legal to
sales and marketing to R&D. In the R&D area, some of the key investments
include clinical studies and investments in formulation sciences and drug
delivery. Managing Product Risk through Life- Cycle Management, Dr. Philip Ma,
Partner, McKinsey & Co.Related term: life cycle management post-genomic:
The genome era is generally regarded to have started on 28 July 1995, with the
publication of the genome of the bacterium Haemophilus influenzae.
["A point of entry into genomics" Nature Genetics 23:273 Nov. 1999]
But the human mitochondrial genome was sequenced in 1981 and published in Nature
290 (5806): 457- 465, Apr. 9, 1981. Sequence
and organization of the human mitochondrial genome by S. Anderson et. al. With an increasing
number of organisms for which we have (more or less) complete genomes we are
beginning to see glimpses of the power of having fully mapped sequences. Still,
in most contexts talk about being "post- genomic" seems a little
premature. "Post Mendelian" seems more accurate as we move from an era
in which genetics has been rooted in monogenic diseases with high penetrance to
a greater awareness (but limited understanding) of polygenic diseases (and
traits) often with relatively low penetrance.
preclinical
drug evaluations:
Preclinical testing of
drugs in experimental animals or in vitro for their biological and toxic
effects and potential clinical applications. MeSH, 1974
preclinical
investigations: Laboratory and animal
studies designed to test the mechanisms, safety, and efficacy of an intervention
prior to its applications to humans [IRB]
precompetitive
research: Several
issues need to be resolved in order to establish a collaborative consortia from
the pharmaceutical company perspective. A major challenge is defining the domain
of precompetitive research. The basic biology, the understanding of disease,
biomarkers of prognosis, and even drug responses all can be areas of
precompetitive R&D, Power said. Pharmaceutical companies have recognized
that they cannot develop a full understanding of these different facets of drug
development on their own.
Establishing
Precompetitive Collaborations to Stimulate Genomics-Driven Product Development:
Workshop Summary. 2011 http://www.ncbi.nlm.nih.gov/books/NBK54320/
predictive
ADME: The completion of the Human Genome Project and
recent advances in our understanding of the molecular mechanisms of diseases
have provided increasing numbers of newly defined biological pathways and
networks with potential preventive or therapeutic targets. The development of
molecular diversity libraries and screening of these libraries have provided
tremendous opportunities to discover new chemical and biological agents for the
prevention and treatment of diseases. This created the belief that increasing
numbers of new molecular entities would enter clinical testing and would receive
approval from the Food and Drug Administration (FDA) to treat human disorders.
However, this has not occurred. Many candidate agents are failing during
clinical testing because of their unfavorable pharmacokinetic properties,
unacceptable adverse effects, or major toxicities, as well as the lack of
efficacy.
The
safety of each new chemical entity must be demonstrated prior to its entry into
clinical trials. Investigational New Drug (IND) applications to the FDA require
chemistry, manufacturing, and control information and results from preclinical
toxicology studies for the safety of new agents. Results of nonclinical
pharmacokinetic studies for defining ADME properties, addressing important
safety issues, or assisting the evaluation of toxicology data for
investigational new agents are highly desirable in IND submissions. Novel
preclinical tools for Predictive ADME-Toxicology RFA
Number: RFA-RM-04-023, 2004 http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-023.html#PartI
predictive
safety: Unexpected toxicity is the single greatest
cause of pipeline attrition. Despite the fact that a typical preclinical safety
program will consume about 1,300 rats and 90 dogs, there is no guarantee that
the compound will not present safety problems serious enough to warrant
termination. productivity:
Iain Cockburn, a
professor at the Boston University School of Management who has extensively
studied pharmaceutical research productivity, believes the current dearth of new
drugs is merely an inevitable pause in the industry's development cycle. Today's
drug deficit is often compared with a golden age of applications in the early
1990s that were spawned by advances in small- molecule chemistry 15 to 20 years
earlier, he says. Now the industry is adjusting to a new era of molecular
biology that will take time to produce results. The adjustment,
Cockburn suggests, was side- tracked somewhat by the 1990's biotechnology boom,
which confused the process of drug development as large pharmaceutical firms and
biotech companies sorted out their roles as potential rivals and collaborators.
Further, he says, it is simply harder to invent new drugs now, because the low-
hanging fruit -- such as the once- revolutionary ace inhibitors -- has already
been plucked. "Now the industry is focusing on cancer, Alzheimer, and
exotic viruses. They're working on tougher problems," he says. "The
way you come up with these drugs is through a lot of heavy- duty science rather
than industrial chemistry, and it's just a lot more expensive." Susan
Warner, Pipeline Anxiety: Scientists Pumped into New Roles, Scientist, 17 (10)
May 19, 2003 http://www.the-scientist.com/?articles.view/articleNo/14772/title/Pipeline-Anxiety--Scientists-Pumped-into-New-Roles/
proof of
concept:
Although not suggested by natural language, and in contrast to usage in other
areas, Proof of Principle and Proof of Concept are not synonymous
in drug development. A third term, Proof of Mechanism, is closely related
and is also described here. All of these terms lack rigorous definitions and
exact usage varies between authors, between institutions and over time. The
descriptions given below are intended to be informative and practically useful.[citation needed] Compare proof of
principle. Proof of concept is certainly more prevalent as a term.
Google
2018 Sept 10 Proof of concept over 21 Million, proof of principle over 6
Million, 3 ½ times as many for proof of concept. These two terms are
sometimes used interchangeably, though proof of concept seems generally earlier
than proof of principle. While many of the above examples have a financial
context these terms are also used in more basic research.
Proof of Mechanism or
PoM relates to the earliest stages of drug development, often pre-clinical
(i.e., before trialling the drug on humans, or before trialling with
research animals). It could be based on showing that the drug interacts
with the intended molecular receptor or enzyme, and/or affects cell
biochemistry in the desired manner and direction.
proof of
principle:
Proof of Principle studies are an early stage of clinical drug development when
a compound has shown potential in animal models and early safety testing. This
step of proof-of-principle (PoP) or proof-of-concept (PoC) often links between
Phase-I and dose ranging Phase-II studies. These small-scale studies are
designed to detect a signal that the drug is active on a pathophysiologically
relevant mechanism, as well as preliminary evidence of efficacy in a clinically
relevant endpoint. Sponsors use these studies to estimate whether their compound
might have clinically significant efficacy in other diseases states.
Proof of Principle
studies,
Schmidt B.
Epilepsy Res. 2006 Jan;68(1):48-52.
https://www.ncbi.nlm.nih.gov/pubmed/16377153
Compare proof of
concept
protein
expression:
Protein
expression analysis is undergoing a technological revolution, which will change
the fundamental nature of the data available. ... Current methods for measuring
protein expression are very different from those for measuring gene expression.
Typically, 2D gels are used to separate the proteins from one another, and mass
spectrometry (MS) is then applied to identify the proteins. MS provides
remarkably specific identification of protein fragments, based on their masses.
The masses are then compared with lists of computed masses for identification.
More and more groups are now seeking to bypass 2D gels, using combinations of
protein chips, liquid chromatography, capillary electrophoresis, and mass
spectrometry for protein analysis. proteomics:
The analysis of complete complements of proteins. Proteomics includes not only
the identification and quantification of proteins, but also the determination of
their localization, modifications, interactions, activities, and, ultimately,
their function. Initially encompassing just two- dimensional (2D) gel
electrophoresis for protein separation and identification, proteomics now refers
to any procedure that characterizes large sets of proteins. The explosive growth
of this field is driven by multiple forces - genomics and its revelation of more
and more new proteins; powerful protein technologies, such as newly developed
mass spectrometry approaches, global [yeast] two- hybrid techniques, and
spin-offs from DNA arrays; and innovative computational tools and methods to
process, analyze, and interpret prodigious amounts of data. Stanley Fields
"Proteomics in Genomeland" Science 291: 1221-1224 Feb. 16, 2001
http://www.sciencemag.org/cgi/content/full/291/5507/1221
rational drug discovery:
In contrast to traditional
methods of drug
discovery (known as forward
pharmacology), which rely on trial-and-error testing
of chemical substances on cultured
cells or animals,
and matching the apparent effects to treatments, rational drug design (also
called reverse
pharmacology) begins with a hypothesis that
modulation of a specific biological target may have therapeutic value. In order
for a biomolecule to be selected as a drug target, two essential pieces of
information are required. The first is evidence that modulation of the target
will be disease modifying. This knowledge may come from, for example, disease
linkage studies that show an association between mutations in the biological
target and certain disease states.[15] The
second is that the target is "druggable".
This means that it is capable of binding to a small molecule and that its
activity can be modulated by the small molecule.[16]
Once a suitable target has been identified, the target is normally
cloned and
produced and purified.
The purified protein is then used to establish a screening
assay. In addition, the three-dimensional
structure of the target may be determined. The search for small molecules
that bind to the target is begun by screening libraries of potential drug
compounds. This may be done by using the screening assay (a "wet screen"). In
addition, if the structure of the target is available, a virtual
screen may be performed of candidate drugs.
Ideally the candidate drug compounds should be "drug-like",
that is they should possess properties that are predicted to lead to oral
bioavailability, adequate chemical and
metabolic stability, and minimal toxic effects.[17] Several
methods are available to estimate druglikeness such as Lipinski's
Rule of Five and a range of scoring methods
such as lipophilic
efficiency.[18] Several
methods for predicting drug metabolism have also been proposed in the scientific
literature.[19]
Due to the large number of drug properties that must be simultaneously
optimized during the design process, multi-objective
optimization techniques
are sometimes employed.[20] Finally
because of the limitations in the current methods for prediction of activity,
drug design is still very much reliant on serendipity[21] and bounded
rationality.[22]
Wikipedia accessed 2018 Sept 10
https://en.wikipedia.org/wiki/Drug_design#Rational_drug_discovery
recombinant
DNA technology: A body of techniques for
cutting apart and splicing together different pieces of DNA. When segments of
foreign DNA are transferred into another cell or organism, the substance for
which they code may be produced along with substances coded for by the native
genetic material of the cell or organism. Thus, these cells become
"factories" for the production of the protein coded for by the
inserted DNA. [NIGMS] Related
terms: biotechnology, gene disruption, gene manipulation, genetic
engineering regenerative
medicine: A field of medicine concerned with
developing and using strategies aimed at repair or replacement of damaged,
diseased, or metabolically deficient organs, tissues, and cells via TISSUE
ENGINEERING, CELL TRANSPLANTATION; and ARTIFICIAL ORGANS and BIOARTIFICIAL
ORGANS and tissues. MeSH 2004 research
tools: We
use the term "research tool" in its broadest sense to embrace the full range of
resources that scientists use in the laboratory, while recognizing that from
other perspectives the same resources may be viewed as "end products." For our
purposes, the term may thus include cell lines, monoclonal antibodies, reagents,
animal models, growth factors, combinatorial chemistry libraries, drugs and
drug targets, clones and cloning tools (such as PCR), methods, laboratory
equipment and machines, databases and computer software. .. NIH Working Group on
Research Tools, June 4, 1998
https://www.mmrrc.org/about/NIH_research_tools_policy/
Related term: pre-competitive
resourceome:
Biologist users and scientists approaching the field
do not have a comprehensive index of bioinformatics algorithms, databases, and
literature annotated with information about their context and appropriate use.
We suggest that the full set of bioinformatics resources—the “resourceome”—should
be explicitly characterized and organized. A hierarchical and
machine-understandable organization of the field, along with rich cross-links
(an ontology!) would be a useful start. "Time to organize the
bioinformatics resourceome" Nicola Cannata, Emanuela Merelli, Russ B.
Altman*, PLOS Computational Biology, Dec. 2005 DOI:
10.1371/journal.pcbi.0010076
http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.0010076
ridiculome:
What does it take to turn a ridiculome into a
relevantome? Quality control metrics (recall/precision)
Context specificity Cellular: Is the interaction specific to a
cellular phenotype?
Molecular: Is the interaction dependent on
the availability of other molecular species RNAi RNA
interference: A gene silencing phenomenon whereby
specific dsRNAs (
RNA, DOUBLE- STRANDED) trigger the degradation of homologous mRNA (
RNA, MESSENGER). The specific dsRNAs are processed into SMALL
INTERFERING RNA (siRNA) which serves as a guide for cleavage of the
homologous mRNA in the RNA- INDUCED SILENCING COMPLEX (RISC). DNA METHYLATION
may also be triggered during this process. MeSH 2003
Broader
term: gene silencing robust:
A statistical test that yields approximately correct results despite the
falsity of certain of the assumptions on which it is based Oxford English
Dictionary Hence, can refer to a
process which is relatively insensitive to human foibles and variables in the
way (for example, an assay) is carried out. Idiot- proof.
rules
of five: Lipinski’s rules. Set of
criteria for predicting the oral bioavailability of a compound on the basis of
simple molecular features (molecular weight, CLogP, numbers of
hydrogen- bond donors and acceptors). Often used to profile a library or virtual
library with respect to the proportion of drug- like members which it
contains. IUPAC Combinatorial
An
algorithm, developed by Christopher A. Lipinski (of Pfizer) and
colleagues, in which many of the cutoff numbers are five or multiples of five.
There are actually four rules, and Pfizer has developed a additional number of
criteria for adoption of lead candidates. Advanced Drug Delivery Research 23: 3-
25, 1997.
safety
pharmacology: Pharmacology studies can be divided
into three categories: primary pharmacodynamic, secondary pharmacodynamic, and
safety pharmacology studies. For the purpose of this document, safety
pharmacology studies are defined as those studies that investigate the potential
undesirable pharmacodynamic effects of a substance on physiological functions in
relation to exposure in the therapeutic range and above. ICH Guidance for
Industry, S7A Safety Pharmacology Studies for Human Pharmaceuticals, 2001 http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm074959.pdf
sample
preparation:
The
discussants concluded that the issue of sample preparation and purification has
been sadly neglected at most meetings dealing with proteomics. There was the
impression among some of the discussants that protein biochemists were
developing and using methods to purify proteins that were not being adequately
defined compositionally by mass spectrometrists interested in proteins.
Defining
the Mandate of Proteomics in the Post- Genomics Era, National Academy of
Sciences, 2002 http://www.nap.edu/books/NI000479/html/R1.html
Sample prep isn't
the sexiest job around, but it is one of the most critical. The quality of
isolated nucleic acid and protein samples is critical to generating accurate and
informative data. As genomic and proteomic technologies move in the direction of
higher throughput, upstream sample preparation becomes a potential bottleneck.
Sample capture, transportation, storage, and handling are as critical as
extraction and purification procedures. Obtaining homogenous samples or
isolating individual cells from clinical material is imperative. Standards are
essential. Advances in microfluidic and microarray technologies have further
amplified the need for higher throughput, miniaturized, and automated sample
preparation processes. scaffold
hopping: the definition of scaffold hopping
and, more importantly, the detection of what constitutes a scaffold hop, is also
ill-defined and highly subjective. Essentially, it is agreed that scaffolds
should be substantially different from each other, although significantly
similar to each other, to constitute a hop. In the latter, the scaffolds must
permit a similar geometric arrangement of functional groups to permit the mode
of action. However, this leaves the paradox of how to describe both scaffold
similarity and dissimilarity simultaneously. In this paper, the current statuses
of scaffolds and scaffold hopping are reviewed based on published examples of
scaffold hopping from the literature. An investigation of the degree to which it
is possible to formulate a more rigorous definition of scaffolds and hopping in
the context of molecular topologies is considered. N Brown, E Jacoby, On
scaffolds and hopping in medicinal chemistry. Mini Rev Med Chem 6 (11)
:1217- 1229, Nov 2006 scalable:
Capable of being industrialized and expanded for high- throughput. Analogous to recipes optimized for large
groups, rather than standard recipes being quadrupled or more, with less than
ideal results. Also spelled scaleable. self-assembly:
<biology> A process in which supramolecular hierarchical
organization is established without external intervention.... The approaches
used can be expected to fall into two general categories. The first involves
directly mimicking biological systems or processes to produce materials with
enhanced properties. An example of this approach is the use of molecular
genetic techniques to produce polymers with unprecedentedly uniform molecular
length. The second category involves studying how nature accomplishes a task or
creates a structure with unusual properties, and then applying similar
techniques in a completely different context or using completely different
materials. [Biomolecular self- assembling materials, National Academy of
Sciences 1996] http://www.nas.edu/bpa/reports/bmm/bmm.html#PBMM
Narrower terms:
self-
assembling biomolecular materials, self-assembling peptides. Related terms:
nanoscience
Sentinel
Initiative:
On May 22, 2008, FDA launched the Sentinel Initiative with the
ultimate goal of creating and implementing the Sentinel System--a national,
integrated, electronic system for monitoring medical product safety. The
Sentinel System will enable FDA to query multiple, existing data sources, such
as electronic health record systems and medical claims databases, for
information about medical products. The system will enable FDA to query data
sources at remote locations, consistent with strong privacy and security
safeguards. Data sources will continue to be maintained by their owners.
This historic new system will strengthen FDA's ability to monitor the
performance of a product throughout its entire life cycle. FDA, US http://www.fda.gov/oc/initiatives/advance/sentinel/ sexy
technologies: What makes technologies sexy? It seems
to be a combination of being new, innovative and challenging, affording clever
people a chance to learn new skills (and demonstrate how competitive and bright
they are) and expensive (or otherwise not available to just anyone). A quick
Google search identified artificial intelligence, fuel cells, high- speed
computers, robotics, nanotechnology, Java, smart cards, wireless communications
and biomaterials as "sexy" by some criteria. I'd be interested to hear
other interpretations and nuances of this class of technologies. Are there
significant differences in what biologists, businesspeople, chemists, computer
scientists and others consider "sexy technologies"? single
molecule detection: Recent advances in optical
imaging and biomechanical techniques have demonstrated that it is possible to
make observations on the dynamic behavior of single molecules, to determine
mechanisms of action at the level of an individual molecule, and to explore
heterogeneity among different molecules within a population. These studies have
the potential to provide fundamentally new information about biological
processes and are critical for a better understanding of cellular function.
... Single molecule methods are likely to lead to significant advances in
understanding molecular movement, dynamics, and function. NIGMS, NICDC, NHGRI,
Single Molecule Detection and Manipulation, Feb. 12, 2001 http://grants.nih.gov/grants/guide/pa-files/PA-01-049.html
Broader terms: attomole, femtomole, micromole, nanomole, picomole,
ultrasensitivity, yocto, zeptomole small
molecules: Preferred for drugs as they are orally available (unlike proteins which must be
administered by injection or topically). Size of small molecules is generally
under 1000 Daltons, but many estimates seem to range between 300 to 700 Daltons. SNP Single
nucleotide polymorphism:
SNPs are single base
pair positions in genomic DNA at which different sequence alternatives (alleles)
exist in normal individuals in some population(s), wherein the least frequent
allele has an abundance of 1% or greater. Thus single base insertion/
deletion variants (indels) would not formally be considered to be SNPs.
... In practice, the term SNP is typically used more loosely than required by
the above definition. ... Complications with the above definition also exist.
Specifically, some people might not want to consider disease predisposing single
base variants to be SNPs - but the above definition would encompass such things
as recessively acting, low penetrance, dominant, quantitative trait loci, or
risk associated alleles, since all of these will occur in some normal (non-
diseased) individual. Also the 'some population' component of the
definition is limited by practical challenges of attaining and surveying
representative global population samples. Consequently, claims of non-
polymorphic sequences should always be accompanies by statements of the actual
populations and the numbers of chromosomes tested. Overall, it is therefore
apparent that the term 'SNP' is being widely and imprecisely used as a catch-
all label for many different types of subtle sequence variation. Anthony Brooks
"The essence of SNPs" Gene 234: 177-186, 1999 .
The most common form
of DNA variation, alterations to a single base. If the SNP is in a gene, it can
disrupt the gene's function. Most SNPs do not occur in genes, but can be
associated with other types of DNA variation and so are used effectively as
markers.
A SNP is a position in
the genome where some individuals have one DNA base (e.g., A), and others have a
different base (e.g., C). SNPs and point mutations are structurally identical,
differing only in their frequency. Variations that occur in 1% or less of a
population are considered point mutations, and those occurring in more than 1%
are SNPs. This distinction is pragmatic and reflects the fact that low-
frequency mutations cannot be used effectively in genetic studies as genetic
markers, while more common ones can.
SNPs can occur in
coding regions of the genome (cSNPs), in regulatory regions (rSNPs), or, most
commonly, in "junk DNA" regions, in which case they are referred to as
anonymous SNPs.
specialty
pharmaceuticals:
Every health plan, institution, medical group, pharma/biotech company and
PBM seems to have its own definition, but specialty pharmaceuticals are
generally understood to
be medications that are:* Injectable.
* Indicated for the treatment of chronic -- and often rare --
illnesses. * Expensive -- a single therapy can cost anywhere from $5,000
to $350,000 per patient per year.
That's the simple definition. Beyond these three points, there are
a few additional characteristics that usually apply to specialty
pharmaceuticals:
Non-oral administration. Specialty
drugs are almost always administered by non-oral means (such as injection
or infusion).
Biological origin. Many
specialty products (such as blood products and gene-based therapies) are
manufactured with a biological basis by biotech companies, or by
traditional pharmaceutical companies through biotech divisions or through
business partnerships with biotech companies.
Non-hospital administration. Usually, specialty products
are administered in a non-hospital setting (such as a physician's office,
a clinic or the patient's home).
Reimbursement via the medical
benefit. In managed care, specialty drugs are typically managed
and reimbursed outside of the pharmacy benefit,
usually through the medical benefit.
Special requirements. Specialty medications usually
require special storage and handling (such as refrigeration). They also
demand comprehensive patient education and require continuous monitoring.
The
world of specialty pharma
A look at the value and growth of specialty products
Jun 01, 2005 Tony
Pinsonault
http://www.pharmexec.com/world-specialty-pharma
spheroids and 3d cell culture: It’s
been well established that culturing cells in three-dimensions is much
more representative of the in
vivo environment
than traditional two-dimensional cultures. The multicellular arrangement
allows cells to interact with each other and the extracellular matrix
(ECM), providing a much better understanding of cellular complexities,
particular in cancer and stem cell research Thermo Fisher, Brief History
of Spheroids
stealth
patents: Beware of submarine- stealth genetic
patents, they can be deadly for scientific research. That was the consensus of
genetic patent experts Monday at CHI's Genome Tri-Conference The biggest enemy
of scientific progress, the experts said, are so- called "stealth"
patents -- those which are filed on genes that researchers have located, but
haven't discovered their function. They sit on the patent, sometimes for long
periods of time, during which no research is done. In January [2001], the U.S.
Patent and Trademark Office finalized guidelines forbidding stealth patenting,
but finding these patents will be a long process. Kristen Philipkowski
"New Quest: Mapping Gene Patents" Wired, Mar 6, 2001
Patents
filed on genes
which have been discovered but have unknown function(s). Also known as submarine
patents stem cell
transplantation: The transfer of STEM CELLS from one
individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or
between species (XENOTRANSPLANTATION), or transfer within the same individual
(TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells
determines their potency or pluripotency to differentiate into various cell
types. MeSH 2003
stem cells:
Relatively
undifferentiated cells of the same lineage (family type) that retain the
ability to divide and cycle throughout postnatal life to provide cells that
can become specialized and take the place of those that die or are lost.
Includes Fibroblasts, Hematopoietic Stem Cells, Erythroid Progenitor Cells,
Tumor Stem Cell MeSH, 1984
Alliances are not
always as strategic as hoped.
strategic
investors: affiliates
of corporations that invest on behalf of their parent company STRATEGIC VS.
TRADITIONAL INVESTORS: THE LOWDOWN FROM A VENTURE CAPITAL VET,PAUL
H. LEE, Fast Company Oct 8 2009 http://www.fastcompany.com/
structural
genomics: The discipline of determining
protein structures. It adds critical information in at least two points in the
drug discovery pathway: (1) target identification, or selecting a
pathway in which a drug might function, and (2) medicinal chemistry, or the
actual design of compounds to modulate this pathway. As traditionally
defined, the term structural genomics referred to the use of sequencing and
mapping technologies, with bioinformatic support, to develop complete genome
maps (genetic, physical, and transcript maps) and to elucidate genomic sequences
for different organisms, particularly humans. Now, however, the term is
increasingly used to refer to high- throughput methods for determining protein
structures.
structural
variants: No
two genomes are alike; instead, each displays structural variability in the form
of single-nucleotide polymorphisms (SNPs), deletions or insertions of various
sizes, which are collectively called copy number variants (CNVs) and inversions,
which are copy number neutral structural variants. Nicole Rusk, Finding
copy-number variants, Nature Methods 5(11):917 Nov 2008
Structure
Activity Relationship (SAR):
The
relationship between chemical structure and pharmacological activity for a
series of compounds. IUPAC Medicinal Chemistry
structure
based design:
A design strategy for new chemical
entities based on the three- dimensional (3D) structure of the target
obtained by X-ray or nuclear magnetic resonance (NMR)
studies, or from protein homology models. IUPAC Computational
structure
based drug design: Structure-based design (SBD) has
been in use within the pharmaceutical industry for over twenty-five years. SBD
of compound properties are still developing and growing in acceptance..
synchrotrons:
Devices for accelerating protons or electrons in
closed orbits where the accelerating voltage and magnetic field strength varies
(the accelerating voltage is held constant for electrons) in order to keep the
orbit radius constant. MeSH, 1993
An
important alternative to x-ray crystallography for solving protein structures.
synthetic
biology: Synthetic biology
an
interdisciplinary branch of biology and
engineering.
The subject
combines disciplines from within these domains, such as biotechnology, genetic
engineering, molecular
biology, molecular
engineering, systems
biology, biophysics, electrical
engineering, computer
engineering, control
engineering and evolutionary
biology.
Synthetic biology applies these disciplines to build artificial biological
systems for research, engineering and medical applications….
Synthetic biology is seen differently by biologists and engineers.
Originally seen as part of biology, in recent years the role of electrical
and chemical engineering has become more important.
As usage of the
term has expanded, synthetic biology was recently defined as the
artificial design and engineering of biological systems and living
organisms for purposes of improving applications for industry or
biological research.[7]
In general its purpose can be described as the design and construction of
novel artificial biological pathways, organisms or devices, or the
redesign of existing natural biological systems.
Wikipedia accessed 2018 Feb 27
https://en.wikipedia.org/wiki/Synthetic_biology
Synthetic biology news & research, Nature
https://www.nature.com/subjects/synthetic-biology
systems biology:
is based on the
understanding that the whole is greater than the sum of the parts.
Systems biology has been responsible for some of the most important
developments in the science of human health and environmental
sustainability. It is a holistic approach to deciphering the
complexity of biological systems that starts from the understanding that
the networks that form the whole of living organisms are more than the sum
of their parts. It is collaborative, integrating many scientific
disciplines – biology, computer science, engineering, bioinformatics,
physics and others – to predict how these systems change over time
and under varying conditions, and to develop solutions to the world’s most
pressing health and environmental issues.
target:
Molecules in the body that may be
addressed by drugs to produce a therapeutic effect. (Also used to refer to the
material -- DNA or RNA - that one exposes to the probes on a microarray so that
hybridization can be measured subsequently.
target
identification: Target identification methods
provide a finer degree of detail than target screening and require evidence that
the gene/ protein is correlated with the disease.
target
validation: Demonstrating that a molecular target is
critically involved in a disease process, and that modulation of the target is
likely to have a therapeutic effect. Determining which among
genes or proteins being investigated as potential drug targets lead to
phenotypic changes when modulated, suggesting that they may have value as
therapeutic targets.
Many people would say a
target is truly validated only after proven effective in human trials. The
definition of target validation is clearly evolving, can be seen as
"slippery" and clearly means different things to different
people. text mining:
Using data mining on
unstructured data, such as the biomedical literature.
Text Mining
Glossary, ComputerWorld, 2004 http://www.computerworld.com/article/2564877/business-intelligence/sidebar--text-mining-glossary.html
Includes Categorization, clustering, extraction, keyword search,
natural language processing, taxonomy, and visualization.
tissue
engineering: Generating tissue in
vitro for clinical applications, such as replacing wounded tissues or
impaired organs. A cell culture facility is required for cell harvest and
expansion. MeSH, 2002
The term
"tissue engineering" was coined at an NSF [National Science
Foundation] -sponsored meeting in 1987. At a later NSF- sponsored workshop,
tissue engineering was defined as "...the application of principles and
methods of engineering and life sciences toward fundamental understanding ...and
development of biological substitutes to restore, maintain and improve [human]
tissue functions." This definition is intended to include procedures where
the biological substitutes are cells or combinations of different cells that may
be implanted on a scaffold such as natural collagen or as synthetic,
biocompatible polymers to form a tissue. ["Tissue Engineering"
National Science Foundation] http://www.nsf.gov/od/lpa/nsf50/nsfoutreach/htm/n50_z2/pages_z3/45_pg.htm
top-down: A systems approach, which looks at the big picture and complexity. Genomics is
essentially a top- down approach, the opposite of a bottom- up approach. Our
ways of thinking have been so profoundly influenced by bottom- up, reductionist
approaches that we are having to learn to think in very different ways to begin
to fully exploit genomic data
toxicogenetics: The study of existing genetic knowledge, and the generation of new genetic
data, to understand and thus avoid DRUG TOXICITY and adverse effects from toxic
substances from the environment. MeSH 2004
toxicogenomics: In its strictest definition, refers to the use of DNA microarray technology to
identify patterns of gene expression that can be used to predict human toxicity
of new drug candidates or other potential toxicants. The concept is based on
the hypothesis, proven in only a preliminary sense, that a finite and limited
set of such patterns, or signatures, exists and that these signatures are, in
fact, highly predictive translational
medicine: Recent advances in biological understanding are allowing
pharmaceutical companies to begin to develop tailored therapeutics, thereby
allowing patients to receive the right drug, at the right dose, and at the right
time. However, in order for such treatments to be developed, companies need to
be able to better link data from the laboratory to the clinic (bench to
bedside). This concept is frequently referred to as translational medicine.
Semantic Web Health Care and Life Sciences SIG Charter, 2008 http://www.w3.org/2008/05/HCLSIGCharter#translat
translatome:
The cellular population of proteins expressed in the
organism at a given time, explicitly weighted by their abundance. ... Our
definition of the translatome is partially motivated by the ambiguities in term
proteome, which has two competing definitions. First, broadly favoured by
computational biologists, is a list of all the proteins encoded in the genome
(Gaasterland 1999, Doolittle 2000). In this context, it is equivalent to what
some refer to as the ORFeome, i.e. the set of genes excluding non- coding
regions. Experimentalists, especially those involved in large- scale experiments
such as expression analysis and 2D electrophoresis, favor a second definitions.
Here it is used to describe the actual cellular contents of proteins, taking
into account the different levels of protein concentrations (Yates 2000). We
prefer the former definition for proteome, and use the term translatome for the
later. Dov Greenbaum "Interrelating Different Types of Genomic
Data" Dept. of Biochemistry and Molecular Biology, Yale Univ. 2001 http://bioinfo.mbb.yale.edu/e-print/omes-genomeres/text.pdf
truth: Making
new technology work may be easier than using it to discover truth. Roger Brent,
"Functional genomics: learning to think about gene expression data"
Current Biology 9: R338- R341, 1999
Question
from Nature column Lifelines put to Michel Brunet, palaeontologist "What is
the one thing about science you wish the public understood better?" Answer
"That the 'truth' is always an asymptotic ideal." Dreams of the past,
Nature 423 (6939): 121, 8 May 2003
tumor microenvironment (TME): Consists
of cells, soluble factors, signaling molecules, extracellular matrix, and
mechanical cues that can promote neoplastic transformation, support tumor
growth and invasion, protect the tumor from host immunity, foster
therapeutic resistance, and provide niches for dormant metastases to
thrive. An American Association for Cancer Research (AACR)
special conference held on November 3–6, 2011, addressed five emerging
concepts in our understanding of the TME: its dynamic evolution, how it is
educated by tumor cells, pathways of communication between stromal and
tumor cells, immunomodulatory roles of the lymphatic system, and
contribution of the intestinal microbiota. Tumor
Microenvironment Complexity: Emerging Roles in Cancer Therapy Melody A.
Swartz 1, Noriho
Iida 2, Edward
W. Roberts 3, Sabina
Sangaletti 4, Melissa
H. Wong 5, Fiona
E. Yull6, Lisa M. Coussens 5 , and Yves
A. DeClerck 7 Cancer
Res May 15, 2012 72; 2473 Published
OnlineFirst March
13, 2012; doi: 10.1158/0008-5472.CAN-12-
uncertainty:
The condition in which reasonable knowledge regarding risks,
benefits, or the future is not available. MeSH 2003
The shift to a post-
Mendelian view of genetics (with variable penetrance and eventually, insights
into polygenic diseases) and genomics seems likely to result in more
uncertainty, not less, at least for some time.
venture
philanthropy: https://evpa.eu.com/about-us/what-is-venture-philanthropy As noted in the OECD report, there’s no one
definition or model for “venture philanthropy”—nor is one needed, because
it’s “more of a blanket term, an expression of a more purpose-, results-
and responsibility-driven worldview” many foundations now embrace. The
report did find an “overlapping set of characteristics” that many venture
philanthropy efforts share, although not all occur in every case:
Strategic framing which coordinates targeted
resources (grants and/or investments), so that collectively they create
systemic change; Scales of intervention that address systems and sectors,
rather than individual organizations or projects; Sector focuses that tend
to be cross-sectoral, engaging civil society, markets, and/or governments
as needed; Funding mechanisms that blend grants and investments, as
appropriate to the theory of change; Engagement styles that are more
hands-on, using extended interactions with and sometimes between grantees;
Engagement periods that reflect the goal of systems changes, often five to
ten years rather than one to two years.; Culture and capabilities that are
focused on innovation and experimentation; Monitoring and evaluation that
allows quick adaptation and focuses on outcomes and impacts.
Wait—What is Venture Philanthropy, Again? EILEEN
CUNNIFFE | March
12, 2014
https://nonprofitquarterly.org/2014/03/12/what-is-philanthropist-venture-philanthropy/
Some
patient advocacy groups are investing in companies working on therapeutics in
their areas of interest, and may also help recruit patients for clinical
trials.
virtual
molecules:
It has also
become clear that even the most efficient combinatorial chemistry approaches can
generate only a minute fraction of the 1 x 1040 virtual drug
molecules that could potetially be synthesized. J. Patrick Walters Virtual
Chemical Libraries, 2018
https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.8b01048?src=recsys&journalCode=jmcmar
Resources
IUPAC
definitions are reprinted with the permission of the International Union of Pure
and Applied Chemistry.
Concise
BioPharmaceutical Glossary & Taxonomy
Evolving Terminology for Emerging Technologies
Comments? Questions?
Revisions?
Mary Chitty MSLS
mchitty@healthtech.com
Last revised
July 12, 2019
Alternatively
ADME/Tox. Related terms: bioequivalence, drug disposition, pharmacodynamics, pharmacokinetics
A wide- ranging term encompassing computer applications
that have the ability to make decisions; the ability to explain reasoning
is evidence of intelligence. Also covers methods that have the
ability to learn. J Glassey et al. “Issues in the development of an
industrial bioprocess advisory system” Trends in Biotechnology 18
(4):136-41 April 2000
Includes
blood, vaccines,
tissue, allergenics and biological therapeutics.
See also biological products,
biopharmaceutical
Alternatively/Related/synonymous? terms: biomarkers,
genetic markers, surrogate markers; Broader term: markers Narrower term:
genomic biomarkers
biomolecules:
An organic molecule, part of a living
organism. Includes proteins, DNA, RNA
Integration of genomics (and proteomics) into drug
discovery and development seems likely to be an ongoing process as well.
Related terms:
FIPCO, franchises- pharmaceutical, market fragmentation, multibusters,
pharmaceutical industry
Related terms:
proprietary drug, proprietary name
Synonyms: Drug treatment (drug therapy), medication therapy,
pharmacotherapeutics, pharmacotherapy Genetics Home Reference,
National Library of Medicine, NIH http://ghr.nlm.nih.gov/ghr/glossary/chemotherapy
Clinical
Informatics News http://www.clinicalinformaticsnews.com/
clinical trials:
Pharmacogenomics is a key tool for the design and interpretation of clinical
trials. It contributes to a precise definition of a disease. It has the ability
to correlate drug response to genetic markers and predict dose response and
adverse events in some cases. It allows for representative subject populations
within the clinical trial, and it allows for the stratification of patient
populations. The potential benefits of that include reduction of drug
development time due to the demonstration of efficacy in specific populations;
the optimization of clinical utility by linking sub- types and efficacy; and
reduction of time to market. Other potential benefits include the ability to
differentiate between responder and non- responder populations, which may lead
to a greater likelihood of reimbursement in the end.
Figures and tables http://www.nature.com/nrd/journal/v10/n10/fig_tab/nrd3552_ft.html
CRISPR for Precision Medicine
Developing Accuracy, Speed and Efficiency in Gene Editing and Repair
MARCH 14-15, 2019 San Francisco CA
Gene editing, particularly using the CRISPR (Clustered Regularly
Interspaced Short Palindromic Repeats)/Cas system, has very rapidly
established itself as an important tool in drug discovery and is now being
exploited for therapeutic purposes as well. http://www.triconference.com/Gene-Editing
CRISPR-Cas Systems: Adaptive antiviral defense mechanisms, in
archaea and bacteria, based on DNA repeat arrays called CLUSTERED
REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS (CRISPR elements) that
function in conjunction with CRISPR-ASSOCIATED PROTEINS (Cas proteins).
Several types have been distinguished, including Type I, Type II, and Type
III, based on signature motifs of CRISPR-ASSOCIATED PROTEINS. MeSH Year
introduced: 2014 This comes under Gene Silencing, which comes
under Gene Expression Regulation
Data Lake or data swamp, 2016 https://www.linkedin.com/pulse/data-lake-swamp-kiran-donepudi
Related
term: nonlinear.
ethical drugs:
The old term ethical drugs signified drugs advertised only
to doctors. The expression refers to the original 1847 code of ethics of the
AMA, which deemed advertising directly to the public to be unethical. Over time,
the term came to mean legal drugs. FDAReview.org, Independent Institute http://www.fdareview.org/glossary.shtml#ethical
FDA Drug Approvals and Databases
http://www.fda.gov/cder/rdmt/default.htm
gene editing:
Genetic engineering techniques that involve DNA REPAIR mechanisms for
incorporating site-specific modifications into a cell's genome. MeSH Year
introduced: 2017
Genome editing, or genome editing with engineered nucleases (GEEN) is a
type of genetic
engineering in which DNA is inserted, deleted or replaced in the genome of a living organism using engineered nucleases, or "molecular scissors." These nucleases create site-specific double-strand
breaks (DSBs) at desired locations in
the genome. The induced double-strand breaks are repaired through nonhomologous
end-joining (NHEJ) or homologous
recombination (HR), resulting in targeted mutations ('edits'). As of 2015 there were four families of engineered nucleases
being used: meganucleases, zinc
finger nucleases (ZFNs), transcription
activator-like effector-based nucleases (TALEN), and the clustered regularly interspaced short palindromic repeats
(CRISPR)-Cas system.[1][2][3][4] https://en.wikipedia.org/wiki/Genome_editing Accessed 2017 Oct 18
Broader term:
screening Narrower terms: high content screening, ultra high throughput
screening Related term: high throughput
Narrower terms: bioinformatics; cheminformatics; clinical informatics, molecular
informatics, pharmacoinformatics, protein informatics, research
informatics
Related
terms: antisense, embryonic lethal trait, knockin, knockout, RNAI RNA
Interference Narrower term: genomewide knockdowns
Related terms: ADME,
ADMETox, drug development. Narrower terms: lead discovery, lead
prioritization, lead selection, lead validation, toxicogenomics, parallel
optimization
Narrower terms: cDNA libraries, chemical libraries, combinatorial library,
compound libraries, DNA library, gene library, genomic library, hit optimization
library, lead discovery library, biased libraries, combinatorial antibody
libraries, directed libraries, focused libraries, pool, pool/ split libraries,
sub- library, random libraries, unbiased libraries;
https://www.forbes.com/sites/bernardmarr/2017/05/04/what-is-machine-learning-a-complete-beginners-guide-in-2017/#33c58c2f578f
Alternatively: arrays, gene
chips, SNP chips Related terms: antibody arrays, protein chips
Related terms: CADD Computer Assisted Drug Design, in silico, molecular
graphics, molecular dynamics, virtual screening
Broader term:
antibody Related terms: cloning, hybridoma, fully humanized
antibodies, therapeutic antibodies, polyclonal antibodies
Narrower
terms: nanobiology, nanobiotechnology, nanochemistry, nanoengineering,
nanophysics.
Alternatively nanotechnology Related terms: quantum physics
Related terms:
disruptive technologies, emerging technologies, biocomplexity, complex
Related term: royalty stacking
Related
terms: branched DNA, gene amplification, LCR Ligase Chain Reaction, NASBA.
Narrower terms: nested PCR, OLA, PNA Q-PCR, real time PCR, RT-PCR.
Related
terms : structure based drug design
Combinatorial
Libraries & synthesis: rational library design, computational quantum
chemistry
Links to data (and literature) Links to analysis of
biomedical problems/
Focus on specific features (e.g. mechanisms)
MAGNet Center: Andrea Califano, NCIBI: Brian Athey, Simbios: Russ Altman,
Creating a DBP Community to Enhance the NCBC Biomedical Impact, NCBC Work Group
Report, 18 July 2006 http://www.na-mic.org/Wiki/images/5/52/Systems_WG7.ppt.
Narrower terms: SNPs- human,; anonymous SNPs, cSNPs, candidate SNP, exonic SNPs, intron
SNPs, pSNP, promoter SNPs, rSNP, SNP haplotypes, synonymous SNP.
Related terms: idiomorphism, protein polymorphisms, single amino acid
polymorphisms SAAPS, SNP Consortium, SNP discovery, SNP scans
https://www.thermofisher.com/blog/cellculture/a-brief-history-of-spheroids-and-3d-cell-culture/
Narrower
terms: embryonic stem cells, hematopopoietic stem
cells.
Stem Cell
Glossary,
NIH,
2016 https://stemcells.nih.gov/glossary.htm
Stem cell
research funding, NIH
https://stemcells.nih.gov/funding.htm
strategic
alliances: As the first decade of the 21st century comes to an end,
the pharmaceutical industry is facing a major revenue downturn. The
contributing factors are the expiration of patents on a number of blockbuster
drugs and the stagnant productivity of R&D. As a consequence
generics are expected to seriously erode revenues and the introduction of new
proprietary drugs is not adequate. The once insular pharmaceutical
industry has been forced to look outside beyond its walls for drug pipeline
candidates. The result has been an almost expediential growth of the
past decade in the number and value of strategic alliances. Insight Pharma
Reports
Strategic
Alliances: Synergistic Path to Value Creation 2010
Also known as “strategics”. Many big pharmaceutical companies now
have venture capital arms.
Wikipedia
https://en.wikipedia.org/wiki/Systems_biology
Narrower terms: target characterization, target glut, target
identification, target screening, target validation. Related terms: gene
function, protein function, antisense, hit, lead
Related terms:
clinical proteomics, molecular medicine, translational research
An aggregate of cancer cells
Wikipedia http://en.wikipedia.org/wiki/Venture_philanthropy
Venture Philanthropy: The New Model http://www.kirschfoundation.org/why/venture.html
FDA, Glossary Drugs@FDA, 2012, http://www.fda.gov/cder/drugsatfda/glossary.htm
Glick, David M., Glossary of Biochemistry and Molecular Biology. 2014.
IUPAC International Union of Pure and Applied Chemistry, Glossary of Terms
used in Bioinorganic Chemistry, Recommendations, 1997. 450+ definitions. http://www.chem.qmw.ac.uk/iupac/bioinorg/
King,
Robert C. and William D. Stansfield, Dictionary of Genetics, Oxford
University Press, 8th edition, 2012
MeSH Medical Subject Headings, (PubMed Browser) National Library of Medicine,
Revised annually. 250,000 entry terms, 19,000 main headings. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=MeSH&term=
ORD Office of Rare Diseases NIH Medical & Science Glossaries
https://rarediseases.info.nih.gov/guides/pages/48/medical-and-science-glossaries
Rare diseases
https://rarediseases.info.nih.gov/diseases/browse-by-first-letter/
Pelikan, Edward, Glossary of terms and symbols used in pharmacology, Boston
University Medical School, US, 1993- 1998, about 300 definitions. http://www.bumc.bu.edu/www/busm/pharmacology/
Programmed/framedGlossary.html
Schlindwein Birgid, Hypermedia Glossary of Genetic Terms, 2006. 670
definitions. http://www.weihenstephan.de/~schlind/index.ht
Ethics
How to look for other unfamiliar terms
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