Functional consequences of somatic mutations in cancer using protein pocket-based prioritization approach

摘要: Recently, a number of large-scale cancer genome sequencing projects have generated large volume somatic mutations; however, identifying the functional consequences and roles mutations in tumorigenesis remains major challenge. Researchers identified that protein pocket regions play critical interaction proteins with small molecules, enzymes, nucleic acid. As such, investigating features provides promising approach to new genotype-phenotype relationships cancer. In this study, we developed pocket-based computational uncover We mapped 1.2 million across 36 types from COSMIC database The Cancer Genome Atlas (TCGA) onto over 5,000 three-dimensional structures. further integrated cell line mutation profiles drug pharmacological data Cell Line Encyclopedia (CCLE) order identify putative biomarkers for anticancer responses. found genes harboring were significantly enriched driver genes. Furthermore, tended be highly co-expressed network. Using statistical framework, four (RWDD1, NCF1, PLEK, VAV3), whose expression associated overall poor survival rates melanoma, lung, or colorectal patients. Finally, more likely drug-sensitive drug-resistant. case illustrated BAX gene was sensitivity three drugs (midostaurin, vinorelbine, tipifarnib). This study novel insights into during used might beneficial era precision medicine.