An Automatic Quality Control Pipeline for High-Throughput Screening Hit Identification.
The correction or removal of signal errors in high-throughput screening (HTS) data is critical to the identification of high-quality lead candidates. Although a number of strategies have been previously developed to correct systematic errors and to remove screening artifacts, they are not universally effective and still require fair amount of human intervention. We introduce a fully automated quality control (QC) pipeline that can correct generic interplate systematic errors and remove intraplate random artifacts. The new pipeline was first applied to ~100 large-scale historical HTS assays; in silico analysis showed auto-QC led to a noticeably stronger structure-activity relationship. The method was further tested in several independent HTS runs, where QC results were sampled for experimental validation. Significantly increased hit confirmation rates were obtained after the QC steps, confirming that the proposed method was effective in enriching true-positive hits. An implementation of the algorithm is available to the screening community.
Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA.
Yufeng
Y
Zhai
Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA.
Kaisheng
K
Chen
Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA.
Yang
Y
Zhong
Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA.
Bin
B
Zhou
Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA.
Edward
E
Ainscow
Genomics Research Center, Academia Sinica, Nankang, Taipei, Taiwan.
Ying-Ta
YT
Wu
Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA yzhou@gnf.org.
Yingyao
Y
Zhou
D000465:Algorithms; D016477:Artifacts; D003198:Computer Simulation; D055808:Drug Discovery; D057166:High-Throughput Screening Assays / Q000592:standards*; D006801:Humans; D011786:Quality Control; D013329:Structure-Activity Relationship
automatic quality control; error correction; statistical analyses; structure-activity relationships; ultra-high-throughput screening