SO-Pharm SCOPE: SO-Pharm is a formal ontology that represents domain knowledge in pharmacogenomics. To achieve this goal SO-Pharm articulates ontologies from sub domains of phamacogenomics (i.e. genotype, phenotype, drug, trial representations). SO-Pharm enables to support knowledge about pharmacogenomic hypothesis, case study, and clinical investigations in pharmacogenomics. TODO: - refine free text descriptions of classes - refine property hierarchy Author: Adrien Coulet Version: SO-Pharm 2.0 (alpha version) Release: 09/19/2007 Contact: adrien dot coulet at loria dot fr University of Nancy It is likely that this ontology contains errors, omissions. If you notice any, have suggestions, we would be happy to heard from you. We welcome and appreciate your suggestions. You can send your comments to adrien dot coulet at loria dot fr. SO-Pharm 2.0 (alpha): - towards a complience with OBO Foundry project requierements - prefix SOPHARM added, corresponding to the namespace http://www.loria.fr/~coulet/ontology/sopharm/version2.0/ - mapping with the Relationship Ontology (OBO_REL) - mapping with the Clinical Trial Ontology (CTO, which will become soon OBI for Ontology of Clinical Investigation) - the mapping with the Sequence ontology (SO) has been cleared - MEO participates in the articulation of SO-Pharm and SO heterozygote genotype The patient is heterozygote for the observed allele, i.e.: he presents to different versions of the allele. For a SNP, the item value can be AT, AC, AG, etc. 1 1 1 pharmacogenomic property Created in SO-Pharm 2.0. 18/07/2007 A biological hypothesis of the existence of a relationship between at least one genotype item [SOPHARM_14000], one drug treatment [SOPHARM_23100] and one phentoype item[SOPHARM_15000]. chinese chinese people from the HapMap project, for more details see http://www.hapmap.org/citinghapmap.html.en Every clinical item is measured, and should be measured according to a precisly defined method. measurement method A scientifically controlled study of the safety and effectiveness of a therapeutic agent (as a drug or vaccine) using consenting human subjects. Source: www.m-w.org In SO-Pharm, a clinical trial is defined by a precise protocole, that should be realize during one or several event, that is done on an selected population (named a panel). clinical trial 1 1 It is a clinical item that informs on the allele the patient presents for a genomic variation. Example: For the genomic variation rs0001, the patient PA_001 presents the genotype "wild" (which has the item value "AA") 1 genomic genotype oceanian People living in the Oceanian Continent. 1 It is a clinical item related to the patient phenotype. It should be quantitative traits as qualitative traits. E. g.: blood pressure. 20070215: new defintion of phenotype item using only QUALITY ontology (new PATO ontology) + UO to be tested for distinction is_magnitude_of (only symbolic) and is_measurment_of (only numeric) 1 1 phenotype item Any hereditary characteristic that is normally associated with some condition but is not a direct symptom of that condition. Source: wiktionary at http://en.wiktionary.org/wiki/endophenotype. It is composed of endophenotype items. endophenotype People living in the American Continent. american vih genotype The genotype observed for a VIH virus. Usually a virus that infects a patient. caucasian caucasian people from the HapMap project, for more details see http://www.hapmap.org/citinghapmap.html.en A regimen of eating and drinking dedicated to modified patient feed behavior. diet ethnic group A population of human individuals whose members identify with each other, either on the basis of a presumed common genealogy or ancestry. Source: Wikipedia, http://en.wikipedia.org/wiki/Ethnicity The particular genotype TPMT*3B for the gene TPMT. tpmt3b The particular genotype TPMT*3C for the gene TPMT. tpmt3c It is measurement method for phenotype item. phenotype measurement method genotype item It is a clinical item bringing information from the patient genome. Example: the genotype of a mutation or of a SNP in a patient. variant allele The observed allele should be the variant one if this one is rare (in the considered population) or if it is considered as an abnormal state of the genome. tpmt3a The particular genotype TPMT*3A for the gene TPMT. clinical trial event A clinical trial event is a moment of the clinical trial when some clinical items are measured. 1 posology The posology of a drug is the specification of the dosage of the drug and of its administration frequency. 1 1 TODO: to link with RXNORM drug A drug. We adopte there the FDCA definition: a drug is a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. E.g.: Methotrexate, Omeprazol, etc. SO-Pharm definition said that a drug is administrated in regard to a drug treatment and add that it is composed of chemical compounds. feed behavior It is a clinical item informing about the way the patient used to eat. E.g.: free-fat diet. A populaton that is involved into a clinical trial according to some criteria (criteria of inclusion). clinical trial panel tpmt1 The particular genotype TPMT*1 for the gene TPMT. scientific paper A scientific paper could be any kind of scientific publication (research article, position paper, lettre, book chapter,etc.). A scientific paper could evoke the existence of a pharmacogenomic property [SOPHARM_00100]. normally expressed genotype By opposition to a neoplasmic genotype, it is the genotype that is expressed in physiological conditions. physical treatment It is a treatment based on physical manipulation of the patient body. A human individual. person The exploration of genomic variations in individuals enables the definition of the genotype of individuals. In diploïd organisms, two versions (or two allele) of genes co-exist and both of them must be observed in order to define the genotype.Observed alleles could be the reference allele or a variant allele. For SNP, observed alleles should be two single nuclotides, e.g. A and G. observed allele The phenotype of an individual organism is either its total physical appearance and constitution or a specific manifestation of a trait, such as size, eye color, or behavior that varies between individuals. Source: wikipedia at http://en.wikipedia.org/wiki/Phenotype It is composed of phenotype items. phenotype tpmt genotype The genotype observed for the TPMT gene. known endophenotype item An endophenotype item which has been validated then is known to be involved in endophentoype. smoking behavior Discribing the behavior of a patient in regard to smoking. E. g.: non-smoker. It could be related to a quantity of smoking: x packet year. physical therapy treatment The treatment is based on physical therapy/physiotherapy. viral genotype Viruses from a same species/strain could differs individually in the genome (as indiviudal of any species). In some cases, viral genotype could be associated to the indivdual who hosts the virus. treatment A technique applied onto patient in a view of treating a pathology. potential endophenotype item An item that could be a endophenotype item, but this status is still a supposition. 1 administration frequency 1 The frequence with which a drug or any treatment is administrated to a person (for example to a patient). It is composed of a numerical value and a frequency unit. E.g.: 3 per day (or 3 j^-1), 1 per minute behavior item It is a clinical item relative to the patient behavior. E. g.: The patient behavior in regard to smoking. chemical coumpound Any chemical compound. It should be a component of a drug (active or inactive). It should be a biological chemical compound too (as the cholesterol that is measured during a trial event). life style It describes the life style of the patient. E.g: sedentary, sportsmanlike, etc. Neoplasm could has a variant genotype that differs from the "everwhere else normal genotype" in an individual. neoplasm genotype genotype The genotype is the specific genetic genome of an individual, in the form of DNA. Source: wikipedia at http://en.wikipedia.org/wiki/Genotype There the genotype of an indivdual could be considered, briefly, as a composition of all its genotype items. reference allele The observed allele should be the reference one if this one is observed in most of individual or if it is considered as a normal state of the genome. drug treatment 1 1 A treatmement based on the administration of a (only one) drug according to a (only one) defined posology. It should be a part of a clinical trial protocol or be a patient behavior that must be take into account. family A group of persons belonging to the same family. A group of persons who are living in a definied area of the world. geographically localized population drug dose 1 It describes the dose of one atomic drug administration. It is composed of a numerical value and a unit. E.g: 500 mg, 30 mmol N.b:For constant drug administration (e.g. drip/IV) the drug dose value describe the dose administrate during the reference meantime (e.g. 1 g if the drip is tune at 1g/minute ). The reference meantime is then the administration frequency [SOPHARM_22100], 1 minute in this example. 1 population A group of persons endophenotype item A clinical item related to the patient endophenotype. It is a clinical item that is measured on a family member of the patient. Then it is a same clinical item which is both a simple clinical item for the family member and an endophenotype item for the concerned patient. A disease that as been diagnosed for the concerned patient. E.g.: diabetes. disease diagnostic A human individual involved in a clinical trial or someone who has been subject for the measurement of a clinical item in the frame of a clinical trial (e.g. a family member who is not included in the clinical trial but who is related to an included patient). patient homozygote genotype The patient is homozygote for the observed allele, i.e.: he presents two times the same version of the allele. For a SNP, the item value can be AA, CC, GG or TT. People living in the African Continent. african epigenotype It can refer to reversible, heritable changes in gene regulation that occur without a change in DNA sequence (genotype). Source: wikipedia at http://en.wikipedia.org/wiki/Epigenetics. It is composed of epigentic items. epigenetic item A clinical item related to the patient epigenotype. clinical trial protocol The clinical trial protocole defines one or several clinical trial. It is composed of some measurement methods that are employed for the measurement of clinical item during the trial. It also includes the description of studied treatments. genomic variation Genomic variations are observed modification in the DNA nucleotide sequences between two individuals. E.g.: A SNP, a mutation, a CNV, etc. chromosome variation Do the patient has chromosome variations? i.e.: Any variation in the chromosome number or morphology. yoruba people yoruba people from the HapMap project, for more details see http://www.hapmap.org/citinghapmap.html.en anamnesis The medical history or anamnesis of a patient is information gained by a physician or other healthcare professional by asking specific questions, either of the patient or of other people who know the person and can give suitable information , with the aim of obtaining information useful in formulating a diagnosis and providing medical care to the patient. Source: wikipedia at http://en.wikipedia.org/wiki/Medical_history european People living in the European Continent. People living in the Asian Continent. asian japanese people from the HapMap project, for more details see http://www.hapmap.org/citinghapmap.html.en japanese surgical operation A treatment technique involving the practical application of surgery. clinical item A clinical item is something that is measured on a patient, during a particular clinical event and according to a measuring method. Any variable related to a human individual and measured during a clinical trial is a clinical item. The same clinical item (i.e. the same variable) should be measured on different patients and at different times. Conversely the clinical item must be measured according to only one (or zero) defined method. Otherwise it is another clinical item. Example: the blood pressure - could be measured according to a describe method - could be measured several times (during several clinical events) - could be measured on every patient involved in a study. NB: the value of the measurment while be the value described by the data property "item value" [SOPHARM_01102]. NB: In some cases (e.g. endophenotype) a same clinical item could be both an endophentoype item (i.e. a clinical item) for a patient and a simple clinical item for one of his family members. 1 1 drug behavior It is a clinical item informing about treatments of the patient which are not include in the protocole of the clinical trial. E.g.: antidiabetic treatment in a clinical trial not focusing on antidiabetics effects. genotype measurement method It is measurement method for genotype item. is part of Classical partition object property. is defined by The development of clinical trial is guided by the clinical trial protocol that contains measurment methods, details on patient treatment and constraints for patient inclusion. is measured during A clinical item could be measured during different events. E.g: Blood pressure could be measured during every patient visit. A role describes a specific function or usage for an entity. is the role for interacts with Some biological/chemical entities could interact together. is administrated in Drugs are administrated to patients within drug treatments. is composed of "is composed of" is the inverse of "is part of". It is an aggregation relationship. A scientific paper argues on the existence of an interaction. evokes is measured on relative Since endophenotype items used to be phenotype item measured on relatives, this object property enables to link endophenotype item and the patient on who it is directly measured. is measured according to Each kind of clinical item measured during a trial must be measured according to a defined method in regard to the protocol. If the genotyping of a genomic variation is include in the protocole of a trial, allele observed for this genomic variation will be different depending on individual genomes. E.g: the variation rs0001 has been genotyped as AA and AC. has been genotyped as a clinical trial enrolls various patient independently, and a clinical trial enrolls a clinical trial panel which is the global group of patient included in the trial. enrolls interacts with phentoype Some biological/chemical entities could interact with a phenotype item. is enrolled in Patient could be enrolled in one or several clinical trials. A clinical trial panel, which is composed of patient, is enrolled in only one trial. defines A clinical trial protocol defines how a clinical trial will be developed. has been experimented in An interaction has been experimentated (and potentially proved) on the basis of a clinical trial. interacts with drug treatment Some biological/chemical entities could interact with a drug treatment. An interaction (e.g. a pharmacogenomic property) has been evocated in a scientific paper. has been published in experiments on A clinical study can experiments (or tests or validates) the validity of an interaction. is the moment of measurement of Temporarly, a clinical trial is composed of various "clinical trial events" (visits). During those a list of clinical item are systematically measured for every included patient. E.g: the first visit is moment for the measurement of the blood pressure and the genotype of some genomic variation. A posology is applied to a drug treatment. is the way of administration in on who endophentoype item is measured Relation between a family member of a patient and the endophenotype item which is measured on the family member. Each clinical item is measured according to a defined measurement method. describes measurement of is measured as endophenotype item A clinical item measured on the relative to a included patient could be an enophenotype item for this relative. Each instance of a clinical item is measured on an identified patient. is measured on is the observed genotype for An individual genotype is measured atomically for one genomic variation. The a genomic genotype (into an indivudal, during one event) is observed for a particular genomic variation. Some biological/chemical entities could interact with a genotype item. interacts with genotype is measured as clinical item An endophenotype item for an included patient is a "simple" clinical item for one of its relatives. In that way an endophenotype item measured on the patient x correspond to a clinical item (for instance, a phenotype item) which is actually measured on the patient y who is a relative of x and who could even not been included in the trial. Various entity in relation with the clinicla trial have various role. Example 1: A person who has for role "patientRole" is a patient. Example 2: A treatment has for role "role_in_protocole_application". hasRole Patients presents various clinical item measured during the trial. presents clinical item drug dose value Commercial name of a drug. One drug could have several trade name depending on which pharmaceutical firm sells it. Trade name clinical trial name The name of the clinical trial investigation group Each clinical trial is undertaken by a scientific group which is the investigation group. has drug A drug treatment is composed of only one drug. sex has dose A posology has a dose that define the administrated dose of drug for each time it is administrated (see frequency [SOPHARM_22100]). Name of generic drug. Ex: omeprazol, montelukast. generic name poulation name A given name of the population. Example: Afro-americans administration frequency value patient id A clinical trial enrolls only one clinical trial panel, which is the group of all the patient included in the trial. enrolls panel has posology A drug treatment is composed of a defined posology. A posology has a frequency that define the frequency of the administration of the drug dose. has frequency item value The value of the item. The time form start is the time that is spend form the begin of the study to the current event. Example: For the study visit which is done 3 month after the intitial visit, the time to start is 3 month. TODO: separate the time unity with PATO concepts. time from start Identifier of scientific publication in the NLM PubMed. PMID (PubMed Identifier) is frequency in A frequency composes one part of a posology. A clinical trial panel, which is composed of patient, is enrolled in only one trial. panel is enrolled in is dose in A dose composes one part of a posology.