Pharmacogenomics aims to understand how genetic variation affects the drug response. One key aspect is that this variation leads to a reduced or augmented capacity to metabolize the drug which consequently leads to toxic accumulation or is so rapidly transformed and eliminated that it has no impact.
Biomarkers include chromosomal abnormalities, haplotypes, gene copy numbers, gene variants, and changes in gene expression.
Drugs for which genetic testing is required, recommended, or mentioned
- Warfarin @PharmGKB
- list at PharmGKB
- ADmark® Alzheimer's Evaluation Detects ApoE2, E3, E4 alleles using Restriction Fragment Length Polymorphism (RFLP)
- Drug metabolizing enzyme tests e.g. Cytochrome P450 tests
- PharmGKB - [ PharmGKB @ Bio2RDF]
- dbSNP - SNP data
- Hapmap - genotypes and frequency
- GWAS central - genotype-phenotype assocations
- dbVar - genetic structural variation data (insertions, deletions etc.)
- dbGap - results of studies that have investigated the interaction of genotype and phenotype.
- Gene Expression Omnibus (GEO) -
- Gene Expression Atlas (from ArrayExpress)
- OMIM - diseases, genes
- Personal Genome Project -- Genetic data provided by volunteers
- Genotator -- Aggregated Gene-disease relationship database
- Gen2Phen EU Project
- Leiden Open Variation Database
- Phenome Browser
- Phenex: Ontological Annotation of Phenotypic Diversity
- SO-PHARM - by Adrien Coulet - integrates OBO ontologies and formalizes specific gene variants [paper][ontology]
- Pharmacogenomics Ontology - by Michel Dumontier - represents PharmGKB data in RDF, ontology for measures and outcomes [paper] [ontology ]
- PHARE (PHArmacogenomic RElationships Ontology)- by Adrien Coulet. Proposes concepts and roles to represent relationships of pharmacogenomics interest. Used for text extraction. [paper] [ontology on BioPortal]
- Sequences and genetic variation
- Sequence Ontology (SO)
- OMG SNP - documentXML schema
- ISO 25720:2009 - Genomic Sequence Variation Markup Language (GSVML), based on XML
- SNP Ontology (used by SO-PHARM)
- Other properties of organisms ('phenotypes')
- ICD - (michel)
- CDISC - Clinical Data Interchange Standard
- SNOMED-CT - (bob)
- SNOMED CT is probably the most important clinical coding system. The terms are all concepts, with loose meaning and little modeling. There is vocabulary for describing genetic and genomic data of various kinds, but there appears to be no formal constraint on how one would specify, e.g., a particular SNP.
- Wikipedia has a good description of the semantics in SNOMED, including a brief example of post-coordinated terms. SNOMED logic is restricted to EL++. The 370,000 pre-coordinated codes are atomic, in that, unlike LOINC codes (below), there is no structure to the code itself.
- SNOMED CT User Guide describes the nature of the few relations in SNOMED, in particular the 'isA' hierarchy and the 'interprets' relation.
- Browsing resources include:
- SNOMED CT has a hierarchy of 'isA' terms under 'Clinical finding':
Clinical finding Evaluation finding Genetic finding Gene expression Genetic polymorphism Molecular sequence data and a host of other genetic terms for states, processes, abnormalities, etc.
- Browsing the NCI Metathesaurus, 'Gene expression' has no children. 'Genetic polymorphism' has just one child, a specific polymorphism. There is no actual code for a SNP there.
- Under 'Molecular sequence data' there is a list of possible sequences types, including:
Abnormal amino acid sequence Abnormal carbohydrate sequence... Abnormal nucleotide base sequence... Base sequence... Nucleotide base deletion Nucleotide base sequence... Transcriptional RNA splicing
- Terms like 'Gene expression' and 'Abnormal nucleotide base sequence' bear an 'interprets' relation to 'Genetic test (procedure)'. Note that there are no special codes for concepts like 'abnormal' or 'missing', etc., that can be post-coordinated with other concepts. 'Nucleotide base sequence' appears as a sibling with its 'abnormal' version.
- Current Procedural Terminologyis a non-free resource that is maintained and licensed by Amemerican Medical Association.
- LOINC - Logical Observation Identifiers Names and Codes (matthias)
- LOINC is a standard for representing clinical lab results
- Official website: http://loinc.org/
- LOINC can be searched at http://search.loinc.org/ -- if you search for 'gene' you will see that the current version also contains many identifiers for results of genetic tests.
- LOINC can also be browsed on BioPortal. Puzzling: there seem to be at least two versions of LOINC in there, possibly added to BioPortal by differnt groups. I have not checked in detail how they differ, and how up-to-date they are.
- Number 1: http://bioportal.bioontology.org/ontologies/44774 -- you can browse the class hierarchy at http://bioportal.bioontology.org/visualize/44774
- Number 2: http://bioportal.bioontology.org/ontologies/43063 --- you can browse the class hierarhy at http://bioportal.bioontology.org/ontologies/43063
- The hierarchy of LOINC codes is often based on loose broader/narrower relationships, not true subclass relations.
- The structure of LOINC codes is described at http://loinc.org/faq/getting-started/structure-of-loinc-codes-and-names/
- HL7 clinical genomics (elgar)
-> bosse astrazeneca -> lodd offering (elgar)
EHRs and support for reporting genetic results
- Description of dbSNP in the NCBI handbook
- Information from/about the HGVS nomenclature for the description of sequence variants
- Contains interesting insight into nomenclature, such as "In some disciplines the term "mutation" is used to indicate "a change" while in other disciplines it is used to indicate "a disease-causing change". Similarly, the term "polymorphism" is used both to indicate "a non disease-causing change" or "a change found at a frequency of 1% or higher in the population". To prevent this confusion we do not use the terms mutation and polymorphism (including SNP or Single Nucleotide Polymorphism) but use neutral terms like "sequence variant", "alteration" and "allelic variant"."