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Pharmacogenomics  & Personalized Medicine glossary & taxonomy
Evolving Terminologies for Emerging Technologies
Comments? Questions? Revisions?
Mary Chitty MSLS
Last revised July 09, 2019

SCOPE NOTE There is a lot of overlap between the terms "precision medicine" and "personalized medicine." According to the National Research Council, "personalized medicine" is an older term with a meaning similar to "precision medicine." However, there was concern that the word "personalized" could be misinterpreted to imply that treatments and preventions are being developed uniquely for each individual; in precision medicine, the focus is on identifying which approaches will be effective for which patients based on genetic, environmental, and lifestyle factors. The Council therefore preferred the term "precision medicine" to "personalized medicine." However, some people still use the two terms interchangeably.  Pharmacogenomics is a part of precision medicine. Pharmacogenomics is the study of how genes affect a person’s response to particular drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that are tailored to variations in a person’s genes.  What is the difference between precision medicine and personalized medicine? What about pharmacogenomics? Genetics Home Reference, US NLM, 2018  

Related glossaries include Diagnostics  Biomarkers    Molecular diagnostics    Molecular Medicine      Cancer diagnostics  & therapeutics   Drug safety & pharmacovigilance  Drug targets
Informatics: Drug discovery informatics  Clinical & medical informatics   Technologies  Metabolic engineering & profiling   Microarrays   Sequencing
Biology Expression, gene & protein   Genomics
   SN Ps & genetic variations

ADME: Abbreviation for Absorption, Distribution, Metabolism, Excretion. See also pharmacokinetics, drug disposition. IUPAC Med Chem Also referred to as ADME/ Tox ADME/ Toxicology or ADMET

These key properties of pharmaceutical compounds are tested for as part of lead optimization activities. Related terms: DMPK, pharmacokinetics, predictive ADME, toxicogenomics.

Artificial Intelligence for GenomicsPersonalizing Treatments and Cures 2019 April`17-18 Boston MA The role of computer science in modeling cells, analyzing and mapping data networks, and incorporating clinical and pathological data to determine how diseases arise from mutations is becoming more important in genomic medicine. We need to understand where the disease starts and how artificial intelligence delivers genes and pathways for drug targets and diagnostics. The Inaugural AI for Genomics track explores case studies that apply deep learning, machine learning, and artificial intelligence to genomic medicine. We will discuss data curation techniques, text mining approaches, and statistical analytics that utilize deep machine learning to support AI efforts. This will help to integrate omics approaches to discover disease or drug response pathways and identify personalized and focused treatments and cures. 

chronopharmacokinetics: Pharmacokinetic parameters are generally assumed to be invariate with the time of day, although circadian variation of drug metabolism and drug response is known. As proposed, chronopharmacokinetics considers the implications of the chronovariability of pharmacokinetic parameters. In order to investigate chronovariation in the rate of disappearance of a substance from the approximate a linear course until very low blood levels are attained. ... It is concluded that: 1) rhythmicity within elimination curves can only be determined by repetition of the experiment at different times of the diel period; 2)the expectation that a rate-constant estimated at one time of the day may be valid for another part of the day carries with it an unknown risk. No pharmacokinetic analysis can be considered definitive unless chronopharmacokinetic variation of parameters is considered. FM Sturtevant, Chronopharmacokinetics of ethanol. I. Review of the literature and theoretical considerations, Chronobiologia 3(3): 237- 262, Jul-Sept 1976  

chronopharmacology:  The science dealing with the phenomenon of rhythmicity in living organisms is called chronobiology. The branch dealing with the pharmacologic aspects of chronobiology is termed chronopharmacology, which may be subdivided into chronotherapy, chronopharmacokinetics and chronotoxicity. WA Ritschel, H Forusz, Chronopharmacology: a review of drugs studied, Methods Find Exp Clin Pharmacology 16(1): 57- 75, Jan-Feb 1994   

Clinical Pharmacogenetics implementation Consortium One barrier to implementation of pharmacogenetic testing in the clinic is the difficulty in translating genetic laboratory test results into actionable prescribing decisions for affected drugs.  CPIC’s goal is to address this barrier to clinical implementation of pharmacogenetic tests by creating, curating, and posting freely available, peer-reviewed, evidence-based, updatable, and detailed gene/drug clinical practice guidelines. CPIC started as a shared project between PharmGKB and the Pharmacogenomics Research Network (PGRN) in 2009.

clinical pharmacology:   The branch of pharmacology that deals directly with the effectiveness and safety of drugs in humans. MeSH, 1980

Over the past decades, the scope of clinical pharmacology within the pharmaceutical industry has widened considerably. Key growth has been in the area of translational science and exploratory medicine, where clinical pharmacologists are nowadays the mediator between basic research and establishment of clinical usefulness. This role has led to and is supported by the rapid developments in pharmacokinetic-pharmacodynamic modeling and simulation, a strong focus on biomarkers for early informed decision-making, and the advent of pharmacogenomics into safety and efficacy predictions and evaluations. The ultimate goal - safer, more efficacious drug prescription - is shared with that of today's drive for more personalized medicine. This article reviews the evolution of clinical pharmacology within the industry, the regulatory, clinical and societal drivers for this evolution, and the analogy with the establishment of personalized medicine in clinical practice. Clinical pharmacology, biomarkers and personalized medicine: education please. Koning P, Keirns J. Biomark Med. 2009 Dec;3(6):685-700.

computational pharmacology: Our ultimate goal is transforming the process of drug design through the use of advanced computational techniques, particularly machine learning and knowledge- based approaches applied to high throughput molecular biology data. We create novel algorithms for the analysis and interpretation of gene expression arrays, proteomics, metabonomics, and combinatorial chemistry. We also create tools for building, maintaining and applying knowledge- bases of molecular biology, and for knowledge- driven inference from multiple biological data types. Finally, we are developing and applying natural language processing techniques for information extraction from and management of the biomedical literature. The UCHSC Center for Computational Pharmacology, Univ. of Colorado Health Sciences Center, US 

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. Cambridge Healthtech Institute’s Fifth Annual CRISPR for Precision Medicine symposium will bring together scientists and clinicians to talk about the recent progress made in gene editing and its potential going forward. At the same time, they will also discuss what is being done to overcome some of the inherent challenges that exist in terms of guide RNA design, delivery and off-target effects associated with CRISPR/Cas9, and what are some of the alternatives being developed? Experts from pharma/biotech, academic and government labs, and technology/service companies will share their experiences leveraging the utility of CRISPR-based gene editing for diverse applications such as creating cell lines and disease models for functional in vitroin vivo and ex vivo screening that will ultimately pave the way for better and safer therapeutics.
Related terms: Genomic Technologies CRISPR, gene editing

cytochrome P450 enzymes: The most important and well- studied group of drug- metabolizing enzymes, the cytochrome P450 enzymes (found in the liver) are responsible for the metabolism of a large number of pharmaceutical compounds. These enzymes function to detoxify xenobiotics (foreign molecules in the body, including drugs). The various genetic polymorphisms in cytochrome P450 can result in increased enzymatic activity, decreased enzymatic activity, or complete loss of enzyme activity. These changes can, in turn, lead to increased (or decreased) activation of pro- drugs, or to increased (or decreased) metabolism and excretion of drugs. 

disease resistant individuals: Another interesting group [of phenotypes for pharmacogenomics] includes those who have no disease yet have high risk factors.  A classic example are individuals who exposed themselves to multiple risk factors for HIV - unprotected intercourse with multiple partners, intravenous drug use, etc. - and who either did not get the disease, or when they did get it, it progressed very slowly. Interestingly, a gene target was identified in this group - the CCRX deletions.  There are many other disease- resistant groups in medicine. ... In general, disease- resistant groups provide a way of identifying given targets that are pre- validated in human subjects.

DMPK: Drug metabolism and pharmacokinetics.   Related terms: ADME

drug metabolism:  After various consultations, the task group recognized that a tutorial emphasis would be of much more value than just a list of terms with definitions. Advances in ready access to high-quality didactic technical information via the Internet continue to underscore this revelation. The preparation of the additional accompanying tutorials is on-going, including the reformatting of 70 terms. A submission to Pure and Applied Chemistry is expected during 2017. IUPAC Metabolism terms

Drug Metabolizing Enzymes DME:

drug response: Includes drug dispositions (pharmacokinetics, PK) and drug effect (pharmacodynamics, PD). E15 terminology in Pharmacogenomics, ICH,  2008 

Comparison of pharmacogenomics studies will be difficult until a more standard definition of "response" and of various phenotypes can be agreed upon. 

drug response phenotype: SNPs are also useful in pharmacogenomics for matching an individual’s genotype with a drug- response phenotype. It is possible, in this context, to identify individuals who cannot adequately metabolize the drug and must be dosed accordingly, or those with a compromised drug target, who could not benefit from the drug. The discovery of such a relationship will require measuring hundreds of SNPs in or near candidate genes in several thousands of individuals. Validation will require detecting very few SNPs in several hundred to several thousand individuals. These relationships can be used either for clinical trials or diagnostically to determine therapy. Each clinical trial will involve measuring few SNPs in the low thousands of individuals.

drug transporters: Potential drug–drug interactions mediated by the ATP-binding cassette (ABC) transporter and solute carrier (SLC) transporter families are of clinical and regulatory concern. However, the endogenous functions of these drug transporters are not well understood …What are usually considered to be ‘multispecific drug transporters’ come from two transporter superfamilies: the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters1. Because they have a crucial role in absorption, distribution, metabolism and elimination (ADME), these drug transporters are of considerable pharmacological significance…Among the clinical issues driving this heightened focus on drug transporters is the concern about drug–drug interactions at the level of the transporter. Nigam SK. What do drug transporters really do? Nature reviews Drug discovery. 2015;14(1):29-44. doi:10.1038/nrd4461.

expression pharmacogenomics:  Applies genome/proteome scale differential expression technologies to both in vivo and in vitro models of drug response to identify candidate markers correlative with and predictive of drug toxicity and efficacy. It is anticipated to streamline drug development by triaging towards lead compounds and clinical candidates that maximize efficacy while minimizing safety risks. Bonnie E. Gould Rothberg "Use of animal models in expression pharmacogenomic analysis" (Pharmacogenomics Journal 1: 48-58, 2001  Related terms: Expression, genes & more

FDA guidelines: Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations.   check for updates

flip flop pharmacokinetics:  a phenomenon often encountered with extravascularly administered drugs…. Flip-flop occurs when the rate of absorption is slower than the rate of elimination. If it is not recognized, it can create difficulties in the acquisition and interpretation of pharmacokinetic parameters.  Flip-flop pharmacokinetics--delivering a reversal of disposition: challenges and opportunities during drug development. Yanez JA, Remsberg CM, Sayre CL, Forrest ML, Davies NM Ther Deliv 2011 May;2(5):643-72. Broader term: pharmacokinetics

genomic data: PGx [pharmacogenomics] and PGt [pharmacogenetics] research depends on the use of samples to generate data. A harmonised definition for the coding of these samples and their associated data will facilitate use in research and development of new medicines. E15 terminology in Pharmacogenomics, ICH, 2008 E15 Definitions for Genomic Biomarkers, Pharmacogenomics ... - FDA

genomic data samples coding: There are four general categories of coding: identified, coded, anonymised and anonymous. Coded data or samples can be single or double coded. The implications of using a specific data and sample coding category should be considered in the design of PGx [pharmacogenomics] and PGt [pharmacogenetic] research studies. E15 terminology in Pharmacogenomics, ICH, 2008 

genotype-to-phenotype:  Investigators start with a set of genes that are known (or strongly suspected) to be important in modulating the response to drugs, and search for variation in their sequences (that is, their genotype.) Given an understanding of genetic variations, they then search for the phenotype consequences.  Russ Altman "Challenges for Biomedical Informatics and Pharmacogenomics, Stanford Medical Informatics, Annual Review of Pharmacology & Toxicology 2002 April Compare phenotype-to-genotype

immunophenotyping: The recording of observable immunological characteristics of an individual, which result from interaction between the genes of that individual and the environment. [NASA's Neurolab glossary, 1997  

in silico pharmacology:  Bioinformatics is used in drug target identification and validation and in the development of biomarkers and toxicogenomic and pharmacogenomic tools to maximize the therapeutic benefit of drugs. Now that the 'parts list' of cellular signalling pathways is available, integrated computational and experimental programmes are being developed, with the goal of enabling in silico pharmacology by linking the genome, transcriptome and proteome to cellular pathophysiology. PA Whittaker, What is the relevance of bioinformatics to pharmacology? Trends in Pharmacological Sciences. 24 (8): 434- 439, August 2003.   See also under computational pharmacology

individualized medicine: Another term for pharmacogenomics or precision medicine..  One key issue for pharmacogenomics is just how individualized drug therapies are going to become.  There is fundamental tension between the economics of faster and cheaper medical care and customized prescriptions and therapies.  Haplotypes offer hope, as does the tradeoffs between liability for patients likely to encounter adverse events who can be screened out before they take a drug and the prospect of overly fragmented pharmaceutical segments.  

influence-based data mining: See Algorithms & data management  for relevance of this technique to pharmacogenomics data.

integrative and organ systems pharmacology: Bioinformatics and genomic approaches are suggesting new targets for study.  Hypotheses generated by in vitro studies or by computational biology and systems approaches to the integrative behavior of living systems need to be tested in the actual living organism.  The ability to develop genetically modified organisms has outstripped the ability to characterize the phenotypic changes in these organisms.  Interest is growing in behavioral and neurobiological phenomena that can only be studied in relatively intact systems and living organisms.  Discoveries in the areas of chemistry, genomics, and pharmacogenetics have accelerated the rate of research and have increased the demand for integrative and organ systems pharmacologists in the pharmaceutical industry.  Pharmacologists, experienced with in vivo models, form an integral part of every drug discovery and development project and are essential to assuring that only safe and efficacious lead compounds go forward to clinical trials.  New tools, such as microdialysis and imaging methods, have become available that enhance the collection efficiency and value of pharmacological data obtained in vivo.   NIGMS, SHORT COURSE: INTEGRATIVE AND ORGAN SYSTEMS PHARMACOLOGY, Apr 26, 2004, RFA-GM-05-006  See also systems pharmacology

kinetic outliers: Intersubject variability - in particular, the presence of kinetic outliers - is encountered during the course of a drug development program. Often, these outliers can be explained by genetic variability or polymorphism in cytochrome CYP450 genes responsible for drug metabolism. Genetic analysis of outliers could help explain the variability in metabolism and possibly influence the development and labeling of the drug in question.  Related term: pharmacokinetics

LD 50:  The dose of a substance that will kill half (50%) of the treated test animals when given as a single dose.  A measure of acute toxicity. Chemical Hygiene Glossary of Terms, Environment, Health & Safety Lab, Lawrence Berkeley National Laboratory, US

mechanism of action: In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect.[1] A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor.[2] Receptor sites have specific affinities for drugs based on the chemical structure of the drug, as well as the specific action that occurs there. Drugs that do not bind to receptors produce their corresponding therapeutic effect by simply interacting with chemical or physical properties in the body.   Wikipedia accessed 2018 Sept 3   Narrower term: molecular mechanism of action

median effective dose: The dose of a drug predicted (by statistical techniques) to produce a characteristic effect in 50 percent of the subjects to whom the dose is given. The median effective dose (usually abbreviated ED50) is found by interpolation from a dose- effect curve. The ED50 is the most frequently used standardized dose by means of which the potencies of drugs are compared. Although one can determine the dose of drug predicted to be effective in one percent (ED1) or 99 percent (ED99) of a population, the ED50 can be determined more precisely than other similar values. An ED50 can be determined only from data involving all or none (quantal) response; for quantal response data, values for ED0 and ED100 cannot be determined. In analogy to the median effective dose, the pharmacologist speaks of a median lethal dose (LD50), a median anesthetic dose(AD50), a median convulsive dose (CD50), etc. [Edward W. Pelikan, Glossary of terms and symbols used in pharmacology, Boston University Medical School, US, 1993- 1998

metabonomics/metabolomics: In the context of toxicology, this approach involves evaluating tissues and biological fluids for changes in metabolite levels that result from toxicant exposure. In one early manifestation, proton nuclear magnetic resonance (NMR) studies can produce signal patterns representing metabolite mixtures; these patterns can be correlated with toxicant mechanism or identity of affected organs. CHI report Toxicogenomics: The Promise of Safer, Smarter Drug Development,  2002  See also -Omes & -omics  metabolomics, metabonomics

Microbiome-Based Precision Medicine Using the Microbiome as a Tool for Generating Personalized Diagnostics and Therapeutics to Improve Health and Disease MARCH 14-15, 2019 San Francisco CA The microbiome R&D is an area of science that is continuing to prove its importance. A PubMed search on the term “human microbiome” yielded 300 citations in 2003, 4,498 citations in 2013, and 38,318 citations in 2018. Basic and applied biomedical research from the Human Microbiome Project and other independent studies prove that a disruption of a stable microbiome ecosystem results in dysbiosis. This imbalance leads to chronic disease and health conditions like inflammation, metabolic disorders, gut disorders, obesity, type 2 diabetes, autoimmune disorders, inflammatory bowel disease, neurodevelopmental disorders and more. There is great promise in correlating the microbiome compositions with these diseases and using the microbiome as a tool for therapeutic, diagnostic and product development.  See related Molecular Medicine Human Microbiome -Omes microbiome

mode of action MOA: A mode of action (MoA) describes a functional or anatomical change, at the cellular level, resulting from the exposure of a living organism to a substance. In comparison, a mechanism of action (MOA) describes such changes at the molecular level.[1][2]   A mode of action is important in classifying chemicals as it represents an intermediate level of complexity in between molecular mechanisms and physiological outcomes, especially when the exact molecular target has not yet been elucidated or is subject to debate. A mechanism of action of a chemical could be "binding to DNA" while its broader mode of action would be "transcriptional regulation".[3] However, there is no clear consensus and the term mode of action is also often used, especially in the study of pesticides, to describe molecular mechanisms such as action on specific nuclear receptors or enzymes.[4]Wikipedia accessed 2018 Sept 3

The process governing the action of chemicals without the level of detail required to determine mechanism of action  

molecular mechanisms of action: Activities at the molecular level of exogenous compounds affecting normal biochemical pathways, including the actions of PROTEINS; CELL SURFACE RECEPTORS; NEUROTRANSMITTERS; and inhibitors.  MeSH 2004  See also mechanism of action

molecular pharmacology: original applications of biochemistry, biophysics, genetics, and molecular biology juxtaposed with innovative pharmacologic research to elucidate basic problems in pharmacology and toxicology, including areas such as molecular mechanisms involved in drug receptor-effective coupling, xenobiotic metabolism, and antibiotic and anticancer drug action. Molecular Pharmacology journal description Related term: systems pharmacology

molecular phenotyping: The Molecular Phenotyping core provides instrumentation, training, and services for in vitro cell phenotyping.  Specifically, we provide facilities and training for automated nucleic acids purification, microarray analysis, quantitative PCR, and automated immunofluorescence cell marker analysis and screening.  Maine Medical Center Core Facilities Molecular Phenotyping 

network pharmacology: The dominant paradigm in drug discovery is the concept of designing maximally selective ligands to act on individual drug targets. However, many effective drugs act via modulation of multiple proteins rather than single targets. Advances in systems biology are revealing a phenotypic robustness and a network structure that strongly suggests that exquisitely selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy... However, the rational design of polypharmacology faces considerable challenges in the need for new methods to validate target combinations and optimize multiple structure-activity relationships while maintaining drug-like properties. Advances in these areas are creating the foundation of the next paradigm in drug discovery: network pharmacology.  Network pharmacology: the next paradigm in drug discovery, AL Hopkins, Nature Chemical Biology 2008 Nov; 4(11): 682- 690.   

personalized medicine: refers to the tailoring of medical treatment to the individual characteristics of each patient. It does not literally mean the creation of drugs or medical devices that are unique to a patient but rather the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not. –President’s Council of Advisors on Science and Technology (PCAST) September 2008 quoted in The Case for Personalized Medicine   Beth Israel Deaconess Medical Center, Dept of Pathology, Genomic Medicine Initiative

Companion Diagnostics and Other Aspects of Personalized Medicine Focus of this report is the use of personalized medicine for pharmacological/diagnostic combinations; particularly pharmacological therapies and the diagnostic tests, which can provide information on the likelihood of a patient to respond to specific treatments. Historically, drugs have been developed on a “one-size-fits-all” basis, but due to patients responding differently to the same drug and having potentially life-threatening side effects, new therapies have been developed for approaching the treatment of diseases. Such an approach is with personalized medicine.  Personalized medicine is an all-encompassing term for focused treatments in diseases. While in some areas, personalized medicine may focus on an individual’s genome in response to therapy, in others it may be broader and focus on tailoring a medical treatment to the characteristics of each patient.  With personalized medicine becoming a more effective form of treatment, more diagnostic tests are being developed to use in combination with pharmacology. Using this form of treatment, physicians not only target the proper disease with the proper therapy, but patients are also less likely to develop adverse reactions and life-threatening side effects.  Main concepts of personalized medicine  include Various definitions of personalized medicine, Range of disease applications for personalized medicine, Use of personalized medicine in research and development, Technologies used in personalized medicine testing Insight Pharma Reports  Companion Diagnostics and Other Aspects of Personalized Medicine – Overview, 2013

NIH research is working hard to solve the puzzle of how genes and lifestyle connect to affect our lives and our health. Today, researchers can scan and compare entire genomes very quickly. These studies have already turned up disease “signatures” for type 2 diabetes, heart disorders, prostate cancer, Crohn’s disease, Parkinson’s disease, and age-related macular degeneration. More disease-related gene variants are identified every few months.  The Human Genome Project and thousands of follow-on studies are helping scientists to develop gene-targeted treatments. NIH Personalized Medicine  Related terms: individualized medicine, pharmacogenomics , precision medicine

pharmacodynamics: Study of  the biochemical and physiological processes determining the effects of drugs on organisms. Narrower terms: pharmacokinetics;  pharmacodynamic biomarkers, translational pharmacodynamics  Related terms: ADME, mechanism of action, mode of action

pharmacoepigenomics: MGMT hypermethylation demonstrates the possibility of pharmacoepigenomics: methylated tumors are more sensitive to the killing effects of alkylating drugs used in chemotherapy. M Esteller, JG Herman, Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer, Oncogene 23(1): 1-8, Jan 8, 2004 

Not to confuse the semantics even more ...some scientists have begun speculating on whether epigenetic mechanisms might also contribute to drug response, leading to coinage of the terms pharmacoepigenetics and pharmacoepigenomics.  IPR pharmnacogenomics promise Insight Pharma Reports, Pharmacogenomics: Delivering on the Promise, 2009

Epigenomics, official journal of the DNA Methylation Society, Moshe Szyf, editor

pharmacogenetic test: An assay intended to study interindividual variations in DNA sequence related to drug absorption and disposition (pharmacokinetics) or drug action (pharmacodynamics) including polymorphic variation in the genes that encode the functions of transporters, metabolizing enzymes, receptors, and other proteins. Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations. 
Pharmacogenetic tests and genetic tests for inheritable markers: Guidance for Industry and FDA Staff
, CDER,  FDA, 2007 

pharmacogenetics: A subset of pharmacogenomics and is defined as The influence of variations in DNA sequence on drug response. ... does not include other disciplines such as proteomics and metabonomics.  E15 terminology in Pharmacogenomics, ICH, 2008 

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.    See also pharmacogenomics

pharmacogenetics and pharmacogenomics: 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,

Pharmacogenetics has been defined as the study of variability in drug response due to heredity [1]. More recently, with the fashion for adding the suffix ‘… omics’ to areas of research, the term ‘pharmacogenomics’ has been introduced. While the former term is largely used in relation to genes determining drug metabolism, the latter is a broader based term that encompasses all genes in the genome that may determine drug response [2]. The distinction however, is arbitrary and both terms can be used interchangeably.  Pirmohamed M. Pharmacogenetics and pharmacogenomics. British Journal of Clinical Pharmacology. 2001;52(4):345-347. doi:10.1046/j.0306-5251.2001.01498.x.

pharmacogenomic test: An assay intended to study interindividual variations in whole genome or candidate gene, single nucleotide polymorphism SNP maps, haplotype markers, or alterations in gene expression or inactivation that may be correlated with pharmacological function and therapeutic response, In some cases the pattern or profile of change is the relevant biomarker, rather than changes in individual markers.  Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations. 

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

For the purposes of this guidance, the term pharmacogenomics is defined as the use of a pharmacogenomic or pharmacogenetic test (see glossary for definitions) in conjunction with drug therapy. Pharmacogenomics does not include the use of genetic or genomic techniques for the purposes of biological product characterization or quality control (e.g. cell bank characterization, bioassays). The FDA plans to provide guidance on those uses at a future time. Pharmacogenomics also does not refer to data resulting from proteomic or metabolomic techniques.  This document is not meant to provide guidance on pharmacoproteomics or multiplexed protein analyte based technologies. Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations. 

The investigation of variations of DNA and RNA characteristics as related to drug response. ... does not include other disciplines such as proteomics and metabonomics.  E15 terminology in Pharmacogenomics, ICH, 2008 

explores the pharmacogenomic (PGx) realm of personalized medicine, analyzing current R&D and market trends related to the use of genetic information to predict how well patients will respond to certain drugs. Pharmacogenomics is an extremely difficult business, one for which there are no easy answers. Even companies manufacturing and marketing already successful pharmacogenomic drug-test combinations continue to face difficulties. Not the least of the challenges facing pharmacogenomics is scientific. Separating a consistent, predictive association between a SNP or other genetic marker and a drug response phenotype from all the other variables that play into drug response can be next to impossible. Once candidate associations are identified, knowing how to design clinical trials capable of teasing out these associations in the clinic and aligning those trials in preparation for regulatory review create another set of challenges. Insight Pharma Reports, Pharmacogenomics: Delivering on the Promise, 2009

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

Pharmacogenomics history of term  
As explained by de Leon (2009)5 and others, the term pharmacogenetics was reportedly coined in 195910 and was used for many years in reference to genetic differences in pharmacokinetic factors, particularly metabolic enzymes. This history may have something to do with how the FDA continues to define pharmacogenetics, although this is just speculation. Not until the 1990s did the term pharmacogenomics enter the scientific literature. Before then, most research on genetic difference (not just in drug response but with respect to most phenotypes) was limited to differences in DNA sequence. Not until genome-wide technologies emerge and advance did research on the underlying genetic differences in drug response begin to really expand beyond focusing on DNA sequence variation. Even then and now, most of the focus is still on specific DNA sequences, although genome-wide technologies are often used as a first step toward identifying those sequences.  Insight Pharma Reports, Pharmacogenomics: Delivering on the Promise, 2009

Despite their slightly different definitions, as with other "-genetics" and "-genomics" terms, pharmacogenomics (PGt) and pharmacogenomics (PGx) are often used interchangeably.  This is not surprising since both terms refer to the study or use of genetic variation in drug responses. PGx is also often used as the more all-encompassing, or default, term when referring to the general study or use of genetic variation in drug response. ... There really isn't clear consensus (yet) on the best definitions for each term

From pharmacology + genomics.   Narrower term: pharmacogenetics Related terms:  individualized medicine, personalized medicine; Gene definitions    Proteomics  pharmacoproteomics

What is pharmacogenomics?, National Institute of General Medical Sciences, NIH 

Pharmacogenomics (PGx): is defined as: The study of variations of DNA and RNA characteristics as related to drug response. b. Pharmacogenetics ( Pharmacogenetics (PGt) is a subset of pharmacogenomics (PGx) and is defined as: The study of variations in DNA sequence as related to drug response.  E15 PDF] E15 Definitions for Genomic Biomarkers, Pharmacogenomics ... - FDA

Pharmacogenomics Research Network The Pharmacogenomics Research Network, PGRN I–III was funded from 2000 through 2015 by multiple Institutes and Centers of the NIH. The network catalyzed pharmacogenomics discoveries both nationally and internationally through the conduct of collaborative research focused on the discovery and translation of the genetic determinants of drug response, in order to enable safer and more effective drug therapies. A new PGRN, PGRN IV, established July 1, 2015, represents a continuation of these research activities, however in a new model. This new model invites participation of all investigators with an interest in pharmacogenomics research to be part of the new network.

pharmacokinetic- pharmacodynamic relationship:  Quantitative relationship between blood and tissue concentrations of the drug (pharmacokinetics) and the effects (pharmacodynamics) of a drug. J. Kirchheiner et. al, Pharmacogenetics- based therapeutic recommendations - ready for clinical practice? Nature Reviews Drug Discovery, 4 (8): 639- 647, August 2005

pharmacokinetics: Process of the uptake of drugs by the body, the biotransformation they undergo, the distribution of the drugs and their metabolites in the tissues, and the elimination of the drugs and their metabolites from the body. Both the amounts and the concentrations of the drugs and their metabolism are studied. The term has essentially the same meaning as toxicokinetics but the latter term should be restricted to the study of substances other than drugs. IUPAC Compendium

Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance.  MeSH, 1988 Broader terms: DMPK, pharmacodynamics;  Narrower terms: chronopharmacokinetics, flip flop pharmacokinetics, kinetic outliers, pharmacokinetic pharmacodynamic relationship

pharmacological promiscuity:  The term 'pharmacological promiscuity' describes the activity of a single compound against multiple targets. When undesired, promiscuity is a major safety concern that needs to be detected as early as possible in the drug discovery process. The analysis of large datasets reveals that the majority of promiscuous compounds are characterized by recognizable molecular properties and structural motifs, the most important one being a basic center with a pK(a)(B)>6. These compounds interact with a small set of targets such as aminergic GPCRs; some of these targets attract surprisingly high hit rates. Can we discover pharmacological promiscuity early in the drug discovery process? Peters HU, et al Drug Discov Today. 2012 Apr;17(7-8):325-35. Epub 2012 Jan 16. 

pharmacology:  The study of the origin, nature, properties, and actions of drugs and their effects on living organisms. MeSH, 1980 

Used with drugs and exogenously administered chemical substances for their effects on living tissues and organisms. It includes acceleration and inhibition of physiological and biochemical processes and other pharmacologic mechanisms of action. MeSH subheading, 1988  Narrower terms: Computational pharmacology, in silico pharmacology,

pharmacometabonomics:  Pharmaco-metabonomics is defined in the paper as 'the prediction of the outcome (for example, efficacy or toxicity) of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures'. PHG Foundation, Pharmaco-metabonomics & personalized drug treatment, 2006  See also Metabolic engineering & profiling  metabonomics    

pharmacophylogenomics:  This study applied the concept of pharmacophylogenomics, the study of genes, evolution, and drug targets, , to conduct an evolutionary survey of drug targets with respect to their subcellular localizations.  Evolutionary survey of druggable protein targets with respect to their subcellular localizations Xiaotong Wang Genome Biology and Evolution Advance Access published June 7, 2013 doi:10.1093/gbe/evt09 

David B. Searls, Pharmacophylogenomics, Genes, Evolution and Drug Targets, Nature Reviews Drug Discovery 2 ; doi:10.1038/nrd1152, 2003

pharmacoproteomics: Once you have identified a number of proteins secreted in sera or urine, you can segregate the proteins by which are linked to early disease, the onset of metastasis, who does and does not tolerate treatment, toxic effects, and who is prone to resistance or relapse.  Fundamentally, you establish a pharmacoproteomic profile of an individual. Like pharmacogenomics, which allows researchers and clinicians to predict the response of an individual to drug treatment on the basis of his or her genetic profile, the evolving field of pharmacoproteomics allows drug developers and clinicians to further subdivide the treated population.  Randall C. Willis, ":The Matching Game" Modern Drug Discovery, 5(5): 26-35, May 2002

Use of protein expression data to predict toxicity and understand drug mode of action.  

phenotype standards: The characterization of phenotype is important for both the genotype- to- phenotype methods as well as the phenotype - to- genotype methods.  Phenotype is difficult to precisely define, but can be thought of as functional features of gene products, ranging in detail from molecular to the individual and population levels. Unfortunately, phenotype data is not as "digital" as sequence data, and so it is much more difficult to represent.  Nevertheless the success of pharmacogenomics depends on the establishment of standards for describing these data. Russ Altman "Challenges for Biomedical Informatics and Pharmacogenomics, Stanford Medical Informatics, c.2001   

phenotype-to-genotype:  Phenotype- to- genotype approaches take a different approach to pharmacogenomic discovery. Instead of identifying a family of genes in which to characterize genetic variations, investigators search for a phenotypic measure that shows significant variation.  This measure can be a clinical measure (such as the rate of clearance of a drug or the peak level of the drug for a given dose), a cellular measure (the rate of cellular uptake of a drug or the profile of gene expression) or a molecular measure (the enzymatic turnover rate of an enzyme or a substrate binding constant). Russ Altman "Challenges for Biomedical Informatics and Pharmacogenetics, Annual Review of Pharmacology & Toxicology 2002 April  Compare genotype- to- phenotype

physiologically based pharmacodynamics: Physiologically based modelling of pharmacodynamics/toxicodynamics requires an a priori knowledge on the underlying mechanisms causing toxicity or causing the disease. In the context of cancer, the objective of the expert meeting was to discuss the molecular understanding of the disease, modelling approaches used so far to describe the process, preclinical models of cancer treatment and to evaluate modelling approaches developed based on improved knowledge. Modelling the genesis and treatment of cancer: the potential role of physiologically based pharmacodynamics. Steimer JL et. al Eur J Cancer. 2010 Jan;46(1):21-32.

polypharmacology: Drug molecules often interact with multiple targets, coined as polypharmacology, and the unintended drug-target interactions could cause side-effects. Polypharmacology remains to be one of the major challenges in drug development, and it opens novel avenues to rationally design next generation of more effective but less toxic therapeutic agents.  Polypharmacology: drug discovery for the future A. Srinivas Reddy and Shuxing Zhang corresponding author  Expert Rev Clin Pharmacol. Author manuscript; available in PMC 2014 Jan 1. Published in final edited form as:  Expert Rev Clin Pharmacol. 2013 Jan; 6(1): 10.1586/ecp.12.74. doi:  10.1586/ecp.12.74 PMCID: PMC3809828  NIHMSID: NIHMS513387  PMID: 23272792 "dirty drugs" "drug promiscuity" How many drug targets are there?, John P Overington, et. al, Nature Reviews Drug Discovery, 2006 

precision diagnostics: Data volumes from pathology far surpass those from radiology, and 70% of critical medical decisions are based on lab tests, he [Mark Boguski] said. Diagnostic data live in the laboratory information management system (LIMS), not the electronic health record, Boguski argued. But our current diagnostic workhorses—microscopes, dyes used to stain samples, x-ray machines—haven’t changed much since the 19th century. “They aren’t even FDA-approved!” Boguski said. To further the problem, he argued, doctors aren’t trained to properly order and use lab tests. There are redundant tests, inappropriate tests, or results that are misunderstood and misused. The result is real patient harm. #BioIT18: Mark Boguski On Precision Diagnostics And The Launch Of A Population Health Project In Thailand, May 22 2018

precision medicine: According to the Precision Medicine Initiative, precision medicine is "an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person." This approach will allow doctors and researchers to predict more accurately which treatment and prevention strategies for a particular disease will work in which groups of people. It is in contrast to a one-size-fits-all approach, in which disease treatment and prevention strategies are developed for the average person, with less consideration for the differences between individuals. Although the term "precision medicine" is relatively new, the concept has been a part of healthcare for many years. For example, a person who needs a blood transfusion is not given blood from a randomly selected donor; instead, the donor’s blood type is matched to the recipient to reduce the risk of complications. Although examples can be found in several areas of medicine, the role of precision medicine in day-to-day healthcare is relatively limited. Researchers hope that this approach will expand to many areas of health and healthcare in coming years. US National Library of Medicine, Genetics Home Reference, Genomics &* Health Impact blog, What is Precision medicine?
US Centers for Disease Control Precision Medicine
Towards Precision Medicine Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease, National Academies Press, 2011   free PDF

Precision Medicine Toward a Network-based Approach MARCH 11-13, 2019 San Francisco CA Precision medicine continues to progress immensely in the last decade with flourishing discoveries in clinical genetics and genetic epidemiology. These successes have enabled the identification of therapeutic strategies more accurately for patients than ever. Our 4th Annual Precision Medicine program will once again bring together experts in the field to share their knowledge and approaches in moving precision medicine toward routine practice. We will showcase cutting edge technologies and workflow on how to implement precision medicine in different settings along with the adoption of bioinformatics and clinical decision support tools for precision medicine.

predictive pharmacogenomics: Various approaches, including pharmacogenomics, that make up the emerging field of predictive medicine. These approaches allow clinicians to predict the risk of disease based on genetic testing, whether a particular therapy will be effective in a particular patient, the risk of an adverse effect, and the risk that a disease will progress in a particular manner. The technologies underlying these new approaches will change drug discovery and development, clinical trials, and diagnosis and treatment of disease. 

quantitative pharmacology: leverages model-based approaches, operates at both cultural and technical levels to integrate data and scientific disciplines so as to utilize existing knowledge while concomitantly enhancing the ability to make predictions about future experiments and results. Next-generation model-based drug discovery and development: quantitative and systems pharmacology. SR Allerheilgen, Clin Pharmacol Ther 2010 Jul ;88 (1): 135-137. Epub 2010 Jun 9. 

quantitative systems pharmacology: "in the middle of October, Harvard Medical School (HMS) announced a broad initiative in systems pharmacology and NIH released a like-minded white paper, Quantitative and Systems Pharmacology in the Post-genomic Era: New Approaches to Discovering Drugs and Understanding Therapeutic Mechanisms ... what distinguishes systems pharmacology is its laser-like focus on compounds and how they perturb biological systems and pathways. How specifically do compounds—failed and successful drugs as well as others—work in the body? What are the detailed mechanisms? How are they influenced by various ‘omics? How do they vary by tissue? etc. ... The practical implications of such a compound-centric approach are exciting: new targets, new screens, new markers, new understanding of drug failure mechanisms. Indeed sophisticated drug failure analysis may be one of SP’s most promising goals and eventually most rewarding contributions."  What is (Quantitative) Systems Pharmacology? John Russell, BioIT World Jan 2012 issues/2012/jan/what-is- quantitative-systems- pharmacology.html

structural pharmacogenomics: Applying structural genomics toward understanding the consequences of  single nucleotide polymorphisms (SNPs).  .

systems pharmacology: Mechanism-based pharmacokinetic and pharmacodynamics (PKPD) and disease system (DS) models have been introduced in drug discovery and development research, to predict in a quantitative manner the effect of drug treatment in vivo in health and disease.  … Recently systems pharmacology has been introduced as novel approach to predict in vivo drug effects, in which biological networks rather than single transduction pathways are considered as the basis of drug action and disease progression. These models contain expressions to characterize the functional interactions within a biological network. Such interactions are relevant when drugs act at multiple targets in the network or when homeostatic feedback mechanisms are operative. As a result systems pharmacology models are particularly useful to describe complex patterns of drug action (i.e. synergy, oscillatory behavior) and disease progression (i.e. episodic disorders). Systems pharmacology – Towards the modeling of network interactions  lMeindert Danhof  European Journal of Pharmaceutical Sciences  Volume 94, 30 October 2016, Pages 4-14 

therapeutic equivalency:  The relative equivalency in the efficacy of different modes of treatment of a disease, most often used to compare the efficacy of different pharmaceuticals to treat a given disease. MeSH, 1970

therapeutic index TI:   is used to compare the therapeutically effective dose to the toxic dose of a pharmaceutical agent. The TI is a statement of relative safety of a drug. It is the ratio of the dose that produces toxicity to the dose needed to produce the desired therapeutic response. The common method used to derive the TI is to use the 50% dose-response points, including TD50 (toxic dose) and ED50 (effective dose). NLM, Toxtutor

translational pharmacodynamics: Guidance for the use of biomarkers in pharmaceutical development and clinical trial optimization will reduce developmental cycle time. A 'fit-for-purpose' guidance for biomarker use is considered herein when the same biomarker is applied in very different contexts in drug development and after regulatory approval. Recent approved use of renal safety biomarkers in Good Laboratory Practice studies lacks sufficient guidance for the use of these markers across the drug development pipeline. In lead optimization, renal injury biomarkers are possible anchors for promising new prodromal metabolic biomarkers, which are applied before lead candidate selection. A guidance for renal biomarker lead optimization and use in translational pharmacodynamics. Ozer JS. Drug Discov Today. 2010 Feb;15(3-4):142-7. Epub 2009 Dec 21.  Narrower term: pharmacodynamics

Voluntary Genomic Data Submissions VGDS: The designation  for pharmacogenomic data submitted voluntarily to the FDA. Guidance for Industry, Pharmacogenomic Data Submissions CDER, CBER, CDRH, FDA,  March 2005  Non-binding recommendations. 

Pharmacogenomics & Precision Medicine Resources
EMEA, European Medicines Agency, Guidelines on Pharmacogenetics Briefing Meetings, 2008  20 plus definitions 

Genetics Home Reference, What is Pharmacogenomics? 2013

Nature: Personalized medicine

Pelikan, Edward W.  Glossary of terms and symbols used in pharmacology, Boston University Medical School, US, 2004, about 300 definitions.

How to look for other unfamiliar  terms

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.



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