Pruned Machine Learning Models to Predict Aqueous Solubility.

ACS Omega
Alexander L PerrymanJoel S Freundlich

Abstract

Solubility is a key metric for therapeutic compounds. Conversely, insoluble compounds cloud the accuracy of assays at all stages of chemical biology and drug discovery. Herein, we disclose naïve Bayesian classifier models to predict aqueous solubility. Publicly accessible aqueous solubility data were used to create two full, or nonpruned, training sets. These two sets were also combined to create a full fused set, and a training set comprised of a literature collation of solubility data was also considered as a reference. We tested different extents of data pruning on the training sets and constructed machine learning models that were evaluated with two independent, external test sets that contained compounds that were different from the training sets. The best pruned and fused model was significantly more accurate, in comparison to either the full model or the full fused model, with the prediction of these external test sets. By carefully removing data from the training set, less information can be used to create more accurate machine learning models for aqueous solubility. This knowledge and the curated training sets should prove useful to future machine learning approaches.

References

Oct 20, 1975·Biochimica Et Biophysica Acta·B W Matthews
Apr 1, 1997·Journal of Pharmaceutical Sciences·J HuuskonenJ Taskinen
Jun 5, 1998·Journal of Chemical Information and Computer Sciences·J HuuskonenJ Taskinen
Jun 13, 2000·Journal of Chemical Information and Computer Sciences·J Huuskonen
Jun 28, 2000·Pharmaceutical Research·B C Hancock, M Parks
Oct 18, 2001·Journal of Chemical Information and Computer Sciences·Y RanS H Yalkowsky
May 30, 2002·Pharmaceutical Research·Hua GaoPil Lee
May 28, 2003·Journal of Chemical Information and Computer Sciences·Jörg K Wegner, Andreas Zell
Jan 24, 2007·Journal of Chemical Information and Modeling·David S PalmerJohn B O Mitchell
Dec 7, 2007·Journal of Computer-aided Molecular Design·Timon Sebastian SchroeterKlaus-Robert Müller
Feb 15, 2008·Journal of Computer-aided Molecular Design·Olga ObrezanovaMatthew D Segall
May 20, 2008·SAR and QSAR in Environmental Research·J HuuskonenD T Manallack
Dec 6, 2011·Drug Discovery Today·Li DiTakashi Mano
Aug 14, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Christoph Saal, Anna Christine Petereit
Mar 26, 2013·Chemistry & Biology·Sean EkinsJoel S Freundlich
Jun 26, 2013·Journal of Chemical Information and Modeling·Alessandro LusciPierre Baldi
Nov 12, 2013·Nucleic Acids Research·A Patrícia BentoJohn P Overington
Feb 26, 2014·Journal of Chemical Information and Modeling·James L McDonaghJohn B O Mitchell
Sep 25, 2015·Nucleic Acids Research·Sunghwan KimStephen H Bryant
Sep 30, 2015·Pharmaceutical Research·Alexander L PerrymanJoel S Freundlich
Dec 3, 2016·Nucleic Acids Research·Yanli WangJian Zhang
Oct 24, 2017·ACS Medicinal Chemistry Letters·Thomas P StrattonJoel S Freundlich
Jan 10, 2018·Antimicrobial Agents and Chemotherapy·Daigo InoyamaJoel S Freundlich
Jul 1, 2018·Pharmaceutical Research·Alexander L PerrymanJoel S Freundlich

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Citations

Feb 23, 2021·ACS Pharmacology & Translational Science·Haseeb MughalJoel S Freundlich
Jun 29, 2021·SLAS Discovery·Vishal SiramshettyPranav Shah
Sep 30, 2021·Journal of Cheminformatics·Vishwesh Venkatraman

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Methods Mentioned

BETA
solubility assay
light scattering
PCA

Software Mentioned

Studio
Excel
ChEMBL
Pipeline Pilot
Discovery Studio
Discovery

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