2. Academic Validation
  3. A Multi-center Study on the Reproducibility of Drug-Response Assays in Mammalian Cell Lines

A Multi-center Study on the Reproducibility of Drug-Response Assays in Mammalian Cell Lines

  • Cell Syst. 2019 Jul 24;9(1):35-48.e5. doi: 10.1016/j.cels.2019.06.005.
Mario Niepel 1,  Marc Hafner 1,  Caitlin E Mills 1,  Kartik Subramanian 1,  Elizabeth H Williams 1,  Mirra Chung 1,  Benjamin Gaudio 1,  Anne Marie Barrette 2,  Alan D Stern 2,  Bin Hu 2,  James E Korkola 3,  LINCS Consortium,   Joe W Gray 3,  Marc R Birtwistle 4,  Laura M Heiser 5,  Peter K Sorger 6
Affiliations

Affiliations

  • 1 Laboratory of Systems Pharmacology, HMS LINCS Center, Harvard Medical School, Boston, MA 02115, USA.
  • 2 Department of Pharmacological Sciences, Drug Toxicity Signature Generation (DToxS) LINCS Center, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA.
  • 3 Microenvironment Perturbagen (MEP) LINCS Center, OHSU Center for Spatial Systems Biomedicine, Oregon Health & Sciences University, Portland, OR 97201, USA.
  • 4 Department of Pharmacological Sciences, Drug Toxicity Signature Generation (DToxS) LINCS Center, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA. Electronic address: [email protected].
  • 5 Microenvironment Perturbagen (MEP) LINCS Center, OHSU Center for Spatial Systems Biomedicine, Oregon Health & Sciences University, Portland, OR 97201, USA. Electronic address: [email protected].
  • 6 Laboratory of Systems Pharmacology, HMS LINCS Center, Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].
PMID: 31302153 DOI: 10.1016/j.cels.2019.06.005
Abstract

Evidence that some high-impact biomedical results cannot be repeated has stimulated interest in practices that generate findable, accessible, interoperable, and reusable (FAIR) data. Multiple papers have identified specific examples of irreproducibility, but practical ways to make data more reproducible have not been widely studied. Here, five research centers in the NIH LINCS Program Consortium investigate the reproducibility of a prototypical perturbational assay: quantifying the responsiveness of cultured cells to anti-cancer drugs. Such assays are important for drug development, studying cellular networks, and patient stratification. While many experimental and computational factors impact intra- and inter-center reproducibility, the factors most difficult to identify and control are those with a strong dependency on biological context. These factors often vary in magnitude with the drug being analyzed and with growth conditions. We provide ways to identify such context-sensitive factors, thereby improving both the theory and practice of reproducible cell-based assays.

Keywords

cancer drugs; cell line; dose response; high[HYPHEN]throughput; microscopy; oncology; pharmacology; reproducibility; screening.

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