Bioinformatics platform for the pharmacogenomic analysis of sequence variation in complex diseases

Traditional studies of complex disease and drug response have utilized a one gene one drug strategy. However because of highthroughput technology , the future trend of personalized medicine lies in understanding and modulating the complex responses involv ing many genes, their sequence variation and the affected drug response. Novel and innovative bioinformatics expert systems are needed in order to provide researchers and clinicians with updated knowledge about the relationships between drugs, diseases a nd gene sequence variation in the form of mutations and single nucleotide polymorphisms (SNPs). Therein is the motivation to build a bioinformatics platform for the new paradigm of pharmacogenomics. In this project we plan to mine information from the me dical literature that establishes knowledge about the relationships between drugs, diseases and sequence variation. The results will be integrated with public databases, making associations critical for the analysis of complex disease. These associations will be analyzed in the context of SNP-Arrays. The project will overcome key challenges in mining of all human sequence variation from the literature and mining for drug knowledge associations from large compound catalogues. The resulting knowedgebase wil l support a software solution to analyze the clustering of SNP-arrays, correlating significant variation from the patient to associations from the knowledgebase. The platform will help researchers and clinicians to gain insights into mechanisms of compl ex diseases such as cancer, as well as provide hypothesis to researchers on drug targets. The project will give the Norwegian FUGE platform access to a powerful bioinformatics system supporting high-throughput experiments within the field of pharmacogenom ics and its trend toward personalized medicine.