Evaluation of Web Service Based Querying of Pharmacogenomics (PGx) Clinical Guidelines Using MyVariant.info, PharmGKB and HGVS Nomenclature

Every year, hundreds of thousands of patients are affected by treatment failure or adverse drug reactions, many of which could be revented by pharmacogenomic testing. To address these deficiencies in care, clinics require automated clinical decision support through computer based systems, which provide clinicians with patient-specific ecommendations. The primary knowledge needed for clinical pharmacogneomics is currently being developed through textual and unstructured guidelines. In this thesis, it is evaluated whether a web service can annotate clinically relevant genetic variants with guideline information using web services and identify areas of challenge. The proposed tool displays a formal representation of pharmacogenomic guideline information through a web service and existing resources. It enables the annotation of variant call format (VCF) files with clinical guideline information from the Pharmacogenomic Knowledge Base (PharmGKB) and Clinical Pharmacogenetics Implementation Consortium (CPIC). The applicability of the web service to nnotate clinically relevant variants with pharmacogenomics guideline information is evaluated by translating five guidelines to a web service workflow and executing the process to annotate publically available genomes. The workflow finds genetic variants covered in CPIC guidelines and influenced drugs. The results show that the web service could be used to annotate in real time clinically relevant variants with up-to-date pharmacogenomics guideline information, although several challenges such as translating variants into star allele nomenclature and the absence of a unique haplotype nomenclature remain before the clinical implementation of this approach and the use on other drugs.