Improved Statistical Methods for Hit Selection in High-Throughput Screening

By C. Brideau, B. Gunter, B. Pikounis, Andy Liaw. Journal of biomolecular screening, 2003

351 citations recorded by the source corpus.

High-throughput screening (HTS) plays a central role in modern drug discovery, allowing the rapid screening of large compound collections against a variety of putative drug targets. HTS is an industrial-scale process, relying on sophisticated auto mation, control, and state-of-the art detection technologies to organize, test, and measure hundreds of thousands to millions of compounds in nano-to microliter volumes. Despite this high technology, hit selection for HTS is still typically done using simple data analysis and basic statistical methods. The authors discuss in this article some shortcomings of these methods and present alternatives based on modern methods of statistical data analysis. Most important, they describe and show numerous real examples from the biologist-friendly Stat Server® HTS application (SHS), a custom-developed software tool built on the commercially available S-PLUS® and StatServer® statistical analysis and server software. This system remotely processes HTS data using powerful and sophisticated statistical methodology but insulates users from the technical details by outputting results in a variety of readily interpretable graphs and tables.

Subfields: Analytical Chemistry, Statistics and Probability

View Paper: https://www.semanticscholar.org/paper/24040338070e36c6b2344d906d03b15b29434725

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Citations in the corpus

• KRAS and YAP1 converge to regulate EMT and tumor survival (2014, methodology): “B-score adjustment was performed for each plate (Brideau et al., 2003), and final score for each ORF was normalized to approximately 40 negative control values on each plate (uninfected wells and wells infected with HcRed, eGFP, BFP, LacZ, or Luciferase).”
• Data-analysis strategies for image-based cell profiling (2017, background): “Ideally, features are normalized across an entire screen in which batch effects are absent; however, normalization within plates is generally performed to correct for batch effects (described in ‘Batch-effect correction’).”