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Cell Syst. 2019 Jul 24;9(1):35-48.e5. doi: 10.1016/j.cels.2019.06.005. Epub 2019 Jul 10.

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

Author information

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: mbirtwi@clemson.edu.
5
Microenvironment Perturbagen (MEP) LINCS Center, OHSU Center for Spatial Systems Biomedicine, Oregon Health & Sciences University, Portland, OR 97201, USA. Electronic address: heiserl@ohsu.edu.
6
Laboratory of Systems Pharmacology, HMS LINCS Center, Harvard Medical School, Boston, MA 02115, USA. Electronic address: peter_sorger@hms.harvard.edu.

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

PMID:
31302153
DOI:
10.1016/j.cels.2019.06.005
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