CellMinerCDB for Integrative Cross-Database Genomics and Pharmacogenomics Analyses of Cancer Cell Lines

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 W Kohn; Cyril H Benes; Mathew Garnett; William C Reinhold; Yves Pommier

doi:10.1016/j.isci.2018.11.029

CellMinerCDB for Integrative Cross-Database Genomics and Pharmacogenomics Analyses of Cancer Cell Lines

iScience. 2018 Dec 21:10:247-264. doi: 10.1016/j.isci.2018.11.029. Epub 2018 Dec 12.

Authors

Vinodh N Rajapakse¹, Augustin Luna², Mihoko Yamade³, Lisa Loman⁴, Sudhir Varma⁴, Margot Sunshine⁵, Francesco Iorio⁶, Fabricio G Sousa⁷, Fathi Elloumi⁵, Mirit I Aladjem⁴, Anish Thomas⁴, Chris Sander⁸, Kurt W Kohn⁴, Cyril H Benes⁹, Mathew Garnett⁶, William C Reinhold⁴, Yves Pommier¹⁰

Affiliations

¹ Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: vinodh.rajapakse@nih.gov.
² cBio Center, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA. Electronic address: augustin_luna@hms.harvard.edu.
³ First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
⁴ Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
⁵ Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA; General Dynamics Information Technology Inc., 3211 Jermantown Road, Fairfax, VA 22030, USA.
⁶ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
⁷ Centro De Estudos Em Células Tronco, Terapia Celular E Genética Toxicológica, Programa De Pós-Graduação Em Farmácia, Universidade Federal De Mato Grosso Do Sul, Campo Grande, MS 79070-900, Brazil.
⁸ cBio Center, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA.
⁹ Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
¹⁰ Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: pommier@nih.gov.

Abstract

CellMinerCDB provides a web-based resource (https://discover.nci.nih.gov/cellminercdb/) for integrating multiple forms of pharmacological and genomic analyses, and 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 exploration of pharmacogenomic determinants and drug signatures. It leverages overlaps of cell lines and drugs across databases to examine reproducibility and expand pathway analyses. We illustrate the value of CellMinerCDB for elucidating gene expression determinants, such as DNA methylation and copy number variations, and highlight complexities in assessing mutational burden. We demonstrate the value of CellMinerCDB in selecting drugs with reproducible activity, expand on the dominant role of SLFN11 for drug response, and present novel response determinants and genomic signatures for topoisomerase inhibitors and schweinfurthins. We also introduce LIX1L as a gene associated with mesenchymal signature and regulation of cellular migration and invasiveness.

Keywords: Bioinformatics; Biological Database; Cancer Systems Biology; Genomics.

Published by Elsevier Inc.

Abstract

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