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
Affiliations
Vinodh N. Rajapakse
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Corresponding author
Augustin Luna
cBio Center, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA; Corresponding author
Mihoko Yamade
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
Lisa Loman
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Sudhir Varma
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Margot Sunshine
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
Francesco Iorio
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK
Fabricio G. Sousa
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
Fathi Elloumi
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
Mirit I. Aladjem
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Anish Thomas
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Chris Sander
cBio Center, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA
Kurt W. Kohn
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Cyril H. Benes
Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA
Mathew Garnett
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK
William C. Reinhold
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Yves Pommier
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Corresponding author
Summary: 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. : Genomics; Bioinformatics; Biological Database; Cancer Systems Biology Subject Areas: Genomics, Bioinformatics, Biological Database, Cancer Systems Biology
