CellMinerCDB for Integrative Genomics and Pharmacogenomics Analyses of Cancer Cell Lines

Abstract

CellMinerCDB provides a web-based resource and portal for integrating multiple forms of pharmacological and genomic analyses, unifying the richest cancer cell line datasets (the NCI-60, NCI-SCLC, Sanger/MGH GDSC, and Broad CCLE/CTRP). CellMinerCDB enables data queries for genomics and gene regulatory network analyses, and identifying pharmacogenomic determinants and drug signatures. It leverages overlaps of cell lines and drugs. A panel of 41 drugs was evaluated in parallel in the NCI-60 and GDSC, supporting reproducibility and further pathway analyses across databases. We demonstrate the value of CellMinerCDB for elucidating gene expression determinants, such as methylation and copy number variation; highlight difficulties in assessing mutation burden; the dominant role of SLFN11 for drug response; novel response determinants and genomic signatures for topoisomerase inhibitors and schweinfurthins; drug repositioning for bisacodyl and acetalax for triple negative breast cancer; and the discovery of LIX1L as a novel mesenchymal gene regulating cancer cellular migration and invasiveness.