Utility-aware screening with clique-oriented prioritization.
Authors | |
Keywords | |
Abstract | Most methods of deciding which hits from a screen to send for confirmatory testing assume that all confirmed actives are equally valuable and aim only to maximize the number of confirmed hits. In contrast, "utility-aware" methods are informed by models of screeners' preferences and can increase the rate at which the useful information is discovered. Clique-oriented prioritization (COP) extends a recently proposed economic framework and aims--by changing which hits are sent for confirmatory testing--to maximize the number of scaffolds with at least two confirmed active examples. In both retrospective and prospective experiments, COP enables accurate predictions of the number of clique discoveries in a batch of confirmatory experiments and improves the rate of clique discovery by more than 3-fold. In contrast, other similarity-based methods like ontology-based pattern identification (OPI) and local hit-rate analysis (LHR) reduce the rate of scaffold discovery by about half. The utility-aware algorithm used to implement COP is general enough to implement several other important models of screener preferences. |
Year of Publication | 2012
|
Journal | J Chem Inf Model
|
Volume | 52
|
Issue | 1
|
Pages | 29-37
|
Date Published | 2012 Jan 23
|
ISSN | 1549-960X
|
URL | |
DOI | 10.1021/ci2003285
|
PubMed ID | 22117901
|
PubMed Central ID | PMC3264765
|
Links | |
Grant list | U54-HG005032 / HG / NHGRI NIH HHS / United States
P50-GM069721 / GM / NIGMS NIH HHS / United States
U54 HG005032 / HG / NHGRI NIH HHS / United States
P50 GM069721-11 / GM / NIGMS NIH HHS / United States
P50 GM069721 / GM / NIGMS NIH HHS / United States
U54 HG005032-05 / HG / NHGRI NIH HHS / United States
|