Efficient modeling and active learning discovery of biological responses

PloS One
Armaghan W NaikRobert F Murphy

Abstract

High throughput and high content screening involve determination of the effect of many compounds on a given target. As currently practiced, screening for each new target typically makes little use of information from screens of prior targets. Further, choices of compounds to advance to drug development are made without significant screening against off-target effects. The overall drug development process could be made more effective, as well as less expensive and time consuming, if potential effects of all compounds on all possible targets could be considered, yet the cost of such full experimentation would be prohibitive. In this paper, we describe a potential solution: probabilistic models that can be used to predict results for unmeasured combinations, and active learning algorithms for efficiently selecting which experiments to perform in order to build those models and determining when to stop. Using simulated and experimental data, we show that our approaches can produce powerful predictive models without exhaustive experimentation and can learn them much faster than by selecting experiments at random.

References

Nov 10, 2001·Annual Review of Genomics and Human Genetics·T IdekerL Hood
Nov 15, 2002·Nature·Hiroaki Kitano
Mar 26, 2003·Journal of Chemical Information and Computer Sciences·Manfred K WarmuthChristian Lemmen
Oct 8, 2004·Nature Biotechnology·Hans V Westerhoff, Bernhard O Palsson
Nov 24, 2004·Journal of Chemical Information and Computer Sciences·Ying Liu
Jan 12, 2005·IEEE Transactions on Pattern Analysis and Machine Intelligence·Pei Chen, David Suter
Mar 21, 2008·Journal of Chemical Information and Modeling·Yukiko FujiwaraRyo Shimizu
Sep 17, 2009·PLoS Computational Biology·Samuel A DanzigerRichard H Lathrop
Mar 5, 2010·BMC Bioinformatics·Thahir P MohamedMadhavi K Ganapathiraju
Jul 6, 2010·Drug Discovery Today·Alejandro MerinoDolores J Cahill
May 19, 2011·Nature Chemical Biology·Robert F Murphy
Nov 15, 2011·Epidemiology·Daniel Westreich
Jan 31, 2012·Journal of Public Health·Brett D Thombs

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Citations

Jun 3, 2014·BMC Bioinformatics·Joshua D KangasRobert F Murphy
Jan 8, 2016·Journal of Chemical Information and Modeling·Tobias LangMatthias Rarey
Apr 29, 2015·Journal of Chemical Information and Modeling·Mateusz MaciejewskiEugen Lounkine
Jul 15, 2015·BMC Bioinformatics·Maja Temerinac-OttRobert F Murphy
Mar 7, 2017·Future Medicinal Chemistry·Daniel RekerJ B Brown
Sep 26, 2019·Angewandte Chemie·Connor W ColeyKlavs F Jensen
Oct 8, 2020·Nature Communications·Xiaokang WangIlias Tagkopoulos

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