Pharmacogenetics Ontology

The Pharmacogenetics Ontology Project is an effort to build and/or integrate one or more taxonomies for the key concepts describing the types of information pertinent to the field of pharmacogenetics. It is inspired by the Gene Ontology, which has helped organize genomic functional annotation. Since pharmacogenetics is a specialized field encompassing particular types of relevant information, we seek a standardized mechanism for organizing and annotating this information to help researchers integrate information about how variation in genotype correlates with the variation in response to drugs.

Our initial focus is to develop a categorization of experimental methodologies used in pharmacogenetics studies, and this is presented below. The methods are color-coded to correspond to the categories of pharmacogenetics knowledge to which they pertain. In this way, researchers can quickly identify types of concepts that are relevant to particular categories of pharmacogenetics information. Members of the Pharmacogenetics Research Network have been identified who are involved in specific domains and their names are listed adjacent to these methods.

Other important taxonomies that are required by the Pharmacogenetics Ontology Project include genes, drugs, and diseases. Currently, PharmGKB uses the HGNC naming scheme for genes, VA/NDFRT vocabulary for drugs, and MeSH hierarchy for diseases.

Categories of Pharmacogenetic Knowledge Color Key

Note: column indentations indicate subcategories.

Pharmacogenetics Ontology	Investigator	Brief Definition
Genotyping Methods		Methods used to determine the genotype of an organism, including sequencing assays and polymorphism detection methods.
Variation Discovery
RFLP
Variation Assessment in Populations
PCR
TaqMan
Phenotyping Methods		Methods used to determine the phenotype of an organism, including assays, clinical measures, and observations.
Molecular and Cellular Phenotyping	Weinshilboum	Assays or measurements of molecular targets or related to the kinetics of molecular components
Enzyme Kinetics	Ratain, Weinshilboum, Giacomini, Flockhart, McLeod	The study of the rate at which an enzyme or transporter functions
Km Measure	Ratain, Giacomini, Flockhart, Weinshilboum	A kinetic parameter used to characterize an enzyme, defined as the concentration of substrate that permits half maximal rate of reaction
Vmax Measure	Ratain, Giacomini, Flockhart, Weinshilboum	The maximum initial velocity of an enzyme catalyzed reaction. I.e. at saturating substrate levels.
Kcat Measure	Ratain, Giacomini	The overall catalytic rate of an enzyme; symbol for turnover number; Vmax divided by the total enzyme concentration.
Ki Measure	Giacomini, Flockhart, Weinshilboum	The dissociation constant of an inhibitor; in enzyme kinetics
T50	Weinshilboum	T50 (temperature at which 50% of the activity is obtained for an enzyme)
Permeability		Measurement of the rate of penetration of a substance through a barrier
Promoter Function Assessment	Weiss, Weinshilboum	This is a general category of experiments related to assessment of the activity of a promoter.
Transcription Factor Detection		Protein/DNA binding reaction to determine whether/which transcription factors might bind to the DNA sequence of interest. Also used to determine if a variant nucleotide disrupts protein binding.
Electrophoresis Mobility Assay		Assay using a radioactively labeled DNA probe to determine whether any proteins bind to the DNA sequence of interest. Non-radioactive probes are used to determine whether protein binding is specific to the sequences or not.
Supershift Assay		Assay where antibody to a protein of interest is added to see whether the protein of interest is participating in the protein binding complex.
Luciferase Reporter Utilization	Ratain, Flockhart, McLeod, Weiss, Weinshilboum	A method for assaying quantitative gene expression.
GFP Tagging	Roden	A molecular tag for measuring the location or expression of a protein.
Protein Half-life		Protein half-life is a measure of the protein turn over rate of a protein in the cell.
Protein Degradation in Rabbit Reticulocyte Lysate		A method to measure the protein half life in vitro, using radiolabeled proteins that are generated in the RRL, and radioactivity is measured on a gel which represents the remaining protein can be compared among each time points, from which half-life can be calculated.
Pulse-chase analysis in cultured cell		A method to measure the protein half-life in the cell system, using cells that are incubated with radiolabeled amino acid, and immunoprecipitation (IP) can be performed using antibody against the protein interested. IP lysates are then run on the gel and radioactivity of the remaining proteins can be measured and compared among each time points.
Protein Complex		Multiple proteins interact with each other to form a complex. It can be a physical interaction, which can have no biological effects, or biological interaction which can interact indirectly. Proteins usually function as complexes rather than as a single one.
Detect Interacting Proteins		Use of biological tools such as immunoprecipitation or proteomics to look at which proteins might interact with the proteins of interest.
Immunoprecipitation		Immunoprecipitation is a way to look at the protein complex or protein-protein interactions.
Proteomics		An unbiased method can help us detect any associated proteins, using LC-MS/MS to separate the cell mixtures or lysates and run through MS/MS to detect all the possible associated proteins.
Heterologous Expression	Weinshilboum	The introduction of a protein into a cell that does not normally express that protein.
Xenopus Expression	Giacomini	Refers to expression of a protein of interest in the Xenopus oocytes
Yeast Expression	Giacomini	Refers to expression of a protein of interest in a yeast expression system.
Mammalian Cell Expression	Flockhart, Roden, Weinshilboum	Refers to expression of a protein of interest in a mammalian cell expression system.
Insect Cell Expression		Refers to expression of a protein of interest in an insect cell expression system.
Single Channel/Transport Measures	Giacomini	Kinetics of transport related to a single channel.
Cellular Uptake Measure	Giacomini, Weinshilboum	Kinetic measures related to the uptake of a substance.
ReceptorKinetics		The study of the rate at which a substrate binds to or acts at a receptor.
Expression Analysis	Ratain, Flockhart, Weiss, Weinshilboum	All methods that assay gene expression.
Spotted Microarrays	Flockhart, Weiss	Microarray experiments in which spotted arrays are used.
Oligonucleotide Arrays	Ratain, Relling, Flockhart, McLeod, Weiss	Microarray experiments containing oligonucleotides
RT PCR	Ratain, Flockhart, McLeod, Weiss, Weinshilboum	A technique for mRNA detection and quantitation.
Transcript Sizing	Ratain	Methods that assess the length of the mRNA transcript.
Protein Arrays		These are microarrays used to detect proteins, monitor their expression levels, and investigate protein interactions and functions.
Antibody-Based Arrays		Microarrays containing antibodies used to assay proteins.
Protein Content/Level		Measurements of the quantity or amount of protein in a cell, space, or assay.
Electrophysiology	Roden, Giacomini	Measurements of the electrical phenomena associated with cardiac or other physiology.
Mass Spectrometry		A technique used to determine the mass, composition, and identity of proteins.
2D Gel Electrophoresis		A method for separating complex mixtures of proteins.
Western Blot	Ratain, Weinshilboum	An antibody-based method for detecting specific proteins
Enzymatic Activity		Measurements of the catalytic action or potency of enzymes, such as measured by enzyme kinetics.
Tissue/Organ Phenotyping	Weinshilboum	All tissue-based methods used to determine the phenotype of an organism.
Tissue Arrays	McLeod	Tissue arrays are glass slides containing spotted tissue samples, used for protein expression studies, antibody screening, tissue-type specificity studies and animal model analyses.
Microsomes	Ratain	Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction.
Liver Microsomes	Ratain, Flockhart, McLeod	Microsomes in liver cells.
Kidney Microsomes		Microsomes in kidney cells.
Lymphocyte Functional Measure	Ratain	These are functional measures of lymphocyte responses
Cytosols	Weinshilboum	Phenotyping methods using cytosolic preparations of tissues (i.e. liver), used in genotype to phenotype (or phenotype to genotype) studies.
Organism Phenotyping		Whole-organism methods used to determine the phenotype of an organism.
Pharmacokinetics Measures	Ratain, Relling, Flockhart, McLeod, Giacomini, Roden	The science and study of the factors which determine the amount of chemical agents at their sites of biological effect at various times after the application of an agent or drug to biological systems. Pharmacokinetics includes study of drug absorption and distribution (biotranslocation), study of the chemical alterations a drug may undergo in the body, (biotransformation), and study of the means by which drugs are stored in the body and eliminated from it.
Plasma Drug Concentrations		The quantity or amount of drug in the blood plasma.
Clearance		The rate of elimination of a drug, metabolite, or other substance from the body or organ of interest.
Clinical Measures		Measurements applied to the whole individual or to samples from that individual.
Laboratory Measures		Measurements applied to samples of blood or tissue from an individual.
Lipid Profile	Krauss, Flockhart	Includes total cholesterol, HDL-cholesterol (often called good cholesterol), LDL-cholesterol (often called bad cholesterol), and triglycerides, and associated computed parameters.
Lipid Profile (Research)	Krauss	A panel of detailed lipid, apolipoprotein, and lipoprotein subspecies measurements used for research purposes.
Coagulation Profile	Flockhart, Roden	Measures the speed of blood coagulation at different steps of the coagulation pathway.
Renin/Angiotensin System Measure	Krauss	Measurements related to the renin/angiotensin system, such as Angiotensinogen, Angiotensin I/II, plasma renin, etc.
Serum Proteomics	Relling	Measurements on proteins in blood serum.
Cell Counts		e.g., CD4 cell counts
Blood Counts of Pathogens		e.g., viremia, fungemia, etc.
Homocysteine Levels		The quantity or amount of homocysteine in the in plasma, CSF, or other fluids.
Physical Measures		Measurements of a physical nature on an individual.
Blood Pressure	O'Connor, Krauss, Roden	Measurement is divided into systolic (pressure during contraction of the heart) and diastolic (pressure during relaxation phase).
Daily BP	O'Connor	The blood pressure, measured daily.
24 Hour BP Monitoring	Krauss	A study recording the blood pressure at intervals during a 24-hour period.
Exercise Response	Roden	Physiological variations that occur when a subject partakes in a defined exercise activity.
Metabolic Measures		These are measurements related to the transformation of substances in the body.
Erythromycin Breath Test		A test measuring the clearance of Erythromycin, and is an indicator of the metabolism of other drugs as well.
EKG	Roden, Flockhart	An recording of the electrical activity of the heart contraction.
QT Interval	Roden, Flockhart	Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole.
PET Scanning		A specialized imaging technique using short lived radioactive substances
Pulmonary Measures		These are laboratory tests related to lung function.
Pulmonary Function Tests	Roden, Flockhart	Measures of how well the lungs take in and exhale air and how efficiently they transfer oxygen into the blood.
FEV1	Weiss	Forced Expiratory Volume in 1 second.
FVC	Weiss	Forced Vital Capacity. This is the total amount of air a subject can blow out forcefully.
Airways Responsiveness Testing with Methacholine	Weiss	A test measuring the bronchial contractility of the airways after administration of Methacholine.
Bone Mineral Density	Flockhart	A nuclear medicine test that estimates the mineralization of bone in a subject.
Cognitive Measures		Assessments of the mental status of a subject.
Hamilton Depression Scale	Licinio, Giacomini	A 17-point screening instrument designed to measure the severity of depression.
Side Effects (Adverse Events)		Undesirable actions of drugs on subject, of all severity.
Hot Flash Occurrences	Flockhart	The sensation of sudden flushing and sweating.
Cancer Treatment-Related Side Effects	Ratain, Relling, Flockhart	All side effects directly attributable to cancer treatment.
Respiratory Depression	Weiss	A decrease in the rate or depth of respiration respiratory effort and decrease in level of alertness.
Bleeding		Emission of blood from anywhere in the body.
GI Bleeding	McLeod	Emission of blood emanating from the gastrointestinal tract.
Thrombocytopenia		A decrease in the number of platelets in the blood
Hepatotoxicity	Ratain, Relling, Flockhart, Krauss	Injury and/or death of liver cells due to a drug or toxin.
Neurotoxicity		Damage, injury, or symptoms related to neural tissues, or abnormal neurological symptoms, often because of drug side-effects.
Thrombosis		Abnormal clotting of blood in a blood vessel, which often results in occlusion of the vessel.
Vasculitis		Inflammation of a vessel, angiitis.
Eosinophilia		The formation and accumulation of an abnormally large number of eosinophils in the blood.
Cholestasis	Flockhart	Arrest of the normal flow of bile.
Angioedema		A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized oedema caused by dilatation and increased permeability of the capillaries and characterized by development of giant wheals.
Myalgia	Krauss	Pain in a muscle or muscles.
Hypotension	Krauss	Abnormally low blood pressure, seen in shock but not necessarily indicative of it.
Fainting	Krauss	A form of syncope (fainting) that occurs as a part of a normal physiologic response to stress (often emotional stress). The individual becomes lightheaded, nauseated, flushed, feels warm and then may lose consciousness for several seconds.
Syncope	Roden	abrupt loss of consciousness, often due to an abnormal rhythm
Seizure		An repetitive, uncontrollable excitation of neural tissue, usually resulting in violent muscular contractions.
Pulmonary Fibrosis	McLeod	Scarring or thickening of tissues deep in the lung.
Outcomes Measures		Evaluation procedures that focus on both the outcome or status (outcome assessment) of the patient at the end of an episode of care - presence of symptoms, level of activity, and mortality; and the process (process assessment) - what is done for the patient diagnostically and therapeutically.
Survival	Ratain, Relling, McLeod, Weinshilboum	An organism living to or beyond a specified time. A time period during which an organism remains alive.
Sudden Death	Roden	An arrhythmogenic death in aortic stenosis, coronary disease, mesothelioma of the AV node, or single coronary artery.
Event Rates For Myocardial Infarction		The frequency of occurrences of medical events or conditions subsequent to heart attacks.
Second Cancers	Ratain, Relling	A cancer different from a cancer originally diagnosed in a patient.
Event-Free Survival		The length of time a subject lives without having one or more complications of a disease.
Relapse Rate	Ratain, McLeod	The rate of recurrence of a disease.
Response Rate	Weiss, McLeod	The rate of cure or response to a disease.
Quality of Life	McLeod	The individuals’ perceptions of their position in life, in the context of the cultural and value systems in which they live and in relation to their goals, expectations, standards and concerns.
Asthma Hospitalization Rate	Weiss	The frequency of occurrences of hospitalizations for acute asthma attacks.
ER Visit Rate	Weiss	The frequency of patient visits the the emergency room.
Atrial Fibrillation	Roden	An abnormal rhythm associated with an irregular heart rate.
Occurrence of Neoplasm	Weinshilboum	A cancer that develops in a patient.

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