PHARMACOGENOMICS OF INTERGENIC SINGLE-NUCLEOTIDE POLYMORPHISMS AND IN SILICO MODELING FOR PRECISION THERAPY

摘要

Functionally altered biological mechanisms arising from disease-associated polymorphisms remain difficult to characterize when those variants are intergenic, or, fall between genes. The present invention uses computational modelling of single-nucleotide polymorphisms (SNPs) drawn from genome-wide association studies (GWAS) or other databases to identify SNP pairs, including SNP pairs where at least one SNP is outside a protein-coding region of a gene, having convergent biological mechanisms. Additional databases, including genomic databases, biological regulatory databases, and databases related to molecular function, are used to further identify and validate the similarity of the biological mechanisms of the SNP pairs. Prioritized SNP pairs having increased similarity of biological mechanisms are then used to identify disease mechanisms, candidate therapeutic drugs, and candidate therapeutic targets among downstream effectors of intergenic SNPs.