Novel Statistical Approach for Primary High-Throughput Screening Hit Selection
- 14 October 2005
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Chemical Information and Modeling
- Vol. 45 (6) , 1784-1790
- https://doi.org/10.1021/ci0502808
Abstract
The standard activity threshold-based method (the “top X” approach), currently widely used in the high-throughput screening (HTS) data analysis, is ineffective at identifying good-quality hits. We have proposed a novel knowledge-based statistical approach, driven by the hidden structure−activity relationship (SAR) within a screening library, for primary hit selection. Application to an in-house ultrahigh-throughput screening (uHTS) campaign has demonstrated it can directly identify active scaffolds containing valuable SAR information with a greatly improved confirmation rate compared to the standard “top X” method (from 55% to 85%). This approach may help produce high-quality leads and expedite the hit-to-lead process in drug discovery.Keywords
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