Dataset Information

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

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.

SUBMITTER: Niepel M

PROVIDER: S-EPMC6700527 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Niepel Mario M Hafner Marc M Mills Caitlin E CE Subramanian Kartik K Williams Elizabeth H EH Chung Mirra M Gaudio Benjamin B Barrette Anne Marie AM Stern Alan D AD Hu Bin B Korkola James E JE Gray Joe W JW Birtwistle Marc R MR Heiser Laura M LM Sorger Peter K PK

Cell systems 20190710 1

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 responsivenes ...[more]

PMID: 31302153

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Project description:BackgroundMulti-site MRI studies are often necessary for recruiting sufficiently sized samples when studying rare conditions. However, they require pooling data from multiple scanners into a single data set, and therefore it is critical to evaluate the variability of quantitative MRI measures within and across scanners used in multi-site studies. The aim of this study was to evaluate the reproducibility of structural and diffusion weighted (DW) MRI measurements acquired on seven scanners at five medical centers as part of the Tuberous Sclerosis Complex Autism Center of Excellence Research Network (TACERN) multisite study.MethodsThe American College of Radiology (ACR) phantom was imaged monthly to measure reproducibility of signal intensity and uniformity within and across seven 3T scanners from General Electric, Philips, and Siemens vendors. One healthy adult male volunteer was imaged repeatedly on all seven scanners under the TACERN structural and DW protocol (5 b = 0 s/mm2 and 30 b = 1000 s/mm2) over a period of 5 years (age 22-27 years). Reproducibility of inter- and intra-scanner brain segmentation volumes and diffusion tensor imaging metrics fractional anisotropy (FA) and mean diffusivity (MD) within white matter regions was quantified with coefficient of variation.ResultsThe American College of Radiology Phantom signal intensity and uniformity were similar across scanners and changed little over time, with a mean intra-scanner coefficient of variation of 3.6 and 1.8%, respectively. The mean inter- and intra-scanner coefficients of variation of brain structure volumes derived from T1-weighted (T1w) images of the human phantom were 3.3 and 1.1%, respectively. The mean inter- and intra-scanner coefficients of variation of FA in white matter regions were 4.5 and 2.5%, while the mean inter- and intra-scanner coefficients of variation of MD in white matter regions were 5.4 and 1.5%.ConclusionOur results suggest that volumetric and diffusion tensor imaging (DTI) measurements are highly reproducible between and within scanners and provide typical variation amplitudes that can be used as references to interpret future findings in the TACERN network.

Dataset Information

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

Publications

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

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