title: mQC: A Heuristic Quality-Control Metric for High-Throughput Drug Combination Screening.
abstract: Quality control (QC) metrics are critical in high throughput screening (HTS) platforms to ensure reliability and confidence in assay data and downstream analyses. Most reported 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. We introduce a predictive, interpretable, matrix-level QC metric, mQC, 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 the plate-level QC metric, Z', mQC provides a more appropriate determination of the quality of a drug combination screen. Retrospective analysis on a number of completed combination screens further shows that mQC is able to identify problematic screens whereas plate-level QC was not able to. In conclusion, our data indicates that mQC is a reliable QC filter that can be used to identify problematic drug combinations 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.
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Wilson
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Goldlust
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Mott
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Eastman
authors.affiliation: National Institute of Allergy and Infectious Diseases (NIAID), Rockville, MD 20852, USA.
authors.forename: Mindy I
authors.initials: MI
authors.lastname: Davis
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: McKnight
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Carleen
authors.initials: C
authors.lastname: Klumpp-Thomas
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Shinn
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute (NCI), Bethesda, MD 20892, USA.
authors.forename: John
authors.initials: J
authors.lastname: Simmons
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Gormally
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Michael
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Thomas
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrer
authors.affiliation: Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), Rockville, MD 20850, USA.
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Guha
mesh_terms: D004338:Drug Combinations; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D011786:Quality Control; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D004338:Drug Combinations; D004364:Pharmaceutical Preparations