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Matrix Combination Screening

mQC: A Quality Control Metric for High-Throughput Combination Screening

Quality control (QC) metrics are critical in high-throughput screening (HTS) platforms to ensure reliability and confidence in assay data and downstream analyses. Most HTS QC metrics are designed for plate-level or single well-level analysis. With the advent of high-throughput combination screening, there is a need for QC metrics that quantify the quality of combination response matrices.

Scientific Synopsis

NCATS introduces mQC, a predictive, interpretable, matrix-level QC metric, based on a mix of data-derived and heuristic features. mQC accurately reproduces the expert assessment of combination response quality and correctly identifies unreliable response matrices that can lead to erroneous or misleading characterization of synergy. When combined with a plate-level QC metric, mQC provides a more appropriate determination of the quality of a drug combination screen.

The analyses indicate that mQC is a reliable QC filter that can be used to identify problematic drug combination matrices and prevent further analysis on erroneously active combinations, as well as for troubleshooting failed screens. The R source code of mQC is available at http://matrix.ncats.nih.gov/mQC.

Publications

Chen L, Wilson K, Goldlust I, Mott BT, Eastman R, Davis MI, Zhang X, McKnight C, Klumpp-Thomas C, Shinn P, Simmons J, Gormally M, Michael S, Thomas CJ, Ferrer M, Guha R. mQC: A heuristic quality-control metric for high-throughput drug combination screening. Sci Rep. 2016;6:37741.

Public Health Impact

The mQC quality control metric ensures that good quality combination screening results are analyzed and followed up. As a result, efforts and resources spent on unreliable or misleading combination responses are minimized. Projects that employ the mQC method should have more reliable outcomes that can be reproduced and form the basis for further development.