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

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
doi: https://doi.org/10.1101/292904
Vinodh N. Rajapakse
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
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  • For correspondence: vinodh.rajapakse@nih.gov aluna@jimmy.harvard.edu
Augustin Luna
2cBio Center, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA
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  • For correspondence: vinodh.rajapakse@nih.gov aluna@jimmy.harvard.edu
Mihoko Yamade
5First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
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  • For correspondence: vinodh.rajapakse@nih.gov aluna@jimmy.harvard.edu
Lisa Loman
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
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Sudhir Varma
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
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Margot Sunshine
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
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Francesco Iorio
3Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
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Fabricio G. Sousa
6Centro 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
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Fathi Elloumi
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
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Mirit I. Aladjem
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
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Anish Thomas
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
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Chris Sander
2cBio Center, Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA
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Kurt Kohn
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
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Cyril H. Benes
4Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Charlestown, Massachusetts, USA.
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Mathew Garnett
3Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
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William C. Reinhold
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
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Yves Pommier
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
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Abstract

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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Posted April 02, 2018.
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Integrative analysis of pharmacogenomics in major cancer cell line databases using CellMinerCDB
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
bioRxiv 292904; doi: https://doi.org/10.1101/292904
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Integrative analysis of pharmacogenomics in major cancer cell line databases using CellMinerCDB
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
bioRxiv 292904; doi: https://doi.org/10.1101/292904

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