Using Cancer Profiles to Identify Synthetic Lethal Therapeutic Targets and Predictive Biomarkers in Cancer Gene Dependency Data

Abstract

Large scale loss-of-function screens utilising CRISPR or siRNA can provide profound insights into the importance of individual genes for the survival of a cancer cell and can drive the identification of therapeutic targets and biomarkers, and the development of targeted drugs. However, the analysis of these data and the substantial bodies of metadata that relate to them, is technically challenging and typically requires substantial expertise in data science and computer coding. To facilitate the analysis of cancer gene dependency data by cancer biologists and clinical scientists, we have developed DepMine - a computational toolkit providing a powerful system for framing complex queries relating cancer gene dependency to the underlying genetic changes that occur in cancer cells. DepMine identifies synthetic lethal relationships between putative target genes and complex cancer profiles built from user-specified combinations of mutations, copy-number variation, and expression levels, and can refine these to optimal biomarker definitions for target dependency.