title: ChemStable: a web server for rule-embedded naïve Bayesian learning approach to predict compound stability.
abstract: Predicting compound chemical stability is important because unstable compounds can lead to either false positive or to false negative conclusions in bioassays. Experimental data (COMDECOM) measured from DMSO/H2O solutions stored at 50 °C for 105 days were used to predicted stability by applying rule-embedded naïve Bayesian learning, based upon atom center fragment (ACF) features. To build the naïve Bayesian classifier, we derived ACF features from 9,746 compounds in the COMDECOM dataset. By recursively applying naïve Bayesian learning from the data set, each ACF is assigned with an expected stable probability (p(s)) and an unstable probability (p(uns)). 13,340 ACFs, together with their p(s) and p(uns) data, were stored in a knowledge base for use by the Bayesian classifier. For a given compound, its ACFs were derived from its structure connection table with the same protocol used to drive ACFs from the training data. Then, the Bayesian classifier assigned p(s) and p(uns) values to the compound ACFs by a structural pattern recognition algorithm, which was implemented in-house. Compound instability is calculated, with Bayes' theorem, based upon the p(s) and p(uns) values of the compound ACFs. We were able to achieve performance with an AUC value of 84% and a tenfold cross validation accuracy of 76.5%. To reduce false negatives, a rule-based approach has been embedded in the classifier. The rule-based module allows the program to improve its predictivity by expanding its compound instability knowledge base, thus further reducing the possibility of false negatives. To our knowledge, this is the first in silico prediction service for the prediction of the stabilities of organic compounds.
authors.affiliation: Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle at University City, Guangzhou, 510006, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.forename: Minghao
authors.initials: M
authors.lastname: Zheng
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.forename: Qiong
authors.initials: Q
authors.lastname: Gu
authors.forename: Johann
authors.initials: J
authors.lastname: Gasteiger
authors.forename: Johan
authors.initials: J
authors.lastname: Tijhuis
authors.forename: Peter
authors.initials: P
authors.lastname: Maas
authors.forename: Jiabo
authors.initials: J
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
mesh_terms: D000465:Algorithms; D001185:Artificial Intelligence; D001499:Bayes Theorem; D003198:Computer Simulation; D004355:Drug Stability; D008956:Models, Chemical