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Integrative analysis of pharmacogenomics in major cancer cell line databases using CellMinerCDB

By Vinodh N. Rajapakse, Augustin Luna, Mihoko Yamade, Lisa Loman, Sudhir Varma, Margot Sunshine, Francesco Iorio, Fabricio G. Sousa, Fathi Elloumi, Mirit I. Aladjem, Anish Thomas, Chris Sander, Kurt Kohn, Cyril H. Benes, Mathew Garnett, William C. Reinhold, Yves Pommier

Posted 02 Apr 2018
bioRxiv DOI: 10.1101/292904

As precision medicine demands molecular determinants of drug response, CellMinerCDB provides (https://discover.nci.nih.gov/cellminercdb/) a web-based portal for multiple forms of pharmacological, molecular, and genomic analyses, unifying the richest cancer cell line datasets (NCI-60, NCI-SCLC, Sanger/MGH GDSC, and Broad CCLE/CTRP). CellMinerCDB enables genomic and pharmacological data queries for identifying pharmacogenomic determinants, drug signatures, and gene regulatory networks for researchers without requiring specialized bioinformatics support. It leverages overlaps of cell lines and tested drugs to allow assessment of data reproducibility. It builds on the complementarity and strength of each dataset. A panel of 41 drugs evaluated in parallel in the NCI-60 and GDSC is reported, supporting drug reproducibility across databases, repositioning of bisacodyl and acetalax for triple negative breast cancer, and identifying novel drug response determinants and genomic signatures for topoisomerase inhibitors and schweinfurthins in development. CellMinerCDB also allowed the identification of LIX1L as a novel mesenchymal gene regulating cellular migration and invasiveness.

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