title: Brainstorming: weighted voting prediction of inhibitors for protein targets.
abstract: The "Brainstorming" approach presented in this paper is a weighted voting method that can improve the quality of predictions generated by several machine learning (ML) methods. First, an ensemble of heterogeneous ML algorithms is trained on available experimental data, then all solutions are gathered and a consensus is built between them. The final prediction is performed using a voting procedure, whereby the vote of each method is weighted according to a quality coefficient calculated using multivariable linear regression (MLR). The MLR optimization procedure is very fast, therefore no additional computational cost is introduced by using this jury approach. Here, brainstorming is applied to selecting actives from large collections of compounds relating to five diverse biological targets of medicinal interest, namely HIV-reverse transcriptase, cyclooxygenase-2, dihydrofolate reductase, estrogen receptor, and thrombin. The MDL Drug Data Report (MDDR) database was used for selecting known inhibitors for these protein targets, and experimental data was then used to train a set of machine learning methods. The benchmark dataset (available at http://bio.icm.edu.pl/∼darman/chemoinfo/benchmark.tar.gz ) can be used for further testing of various clustering and machine learning methods when predicting the biological activity of compounds. Depending on the protein target, the overall recall value is raised by at least 20% in comparison to any single machine learning method (including ensemble methods like random forest) and unweighted simple majority voting procedures.
authors.affiliation: Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Pawinskiego 5a Street, 02-106, Warsaw, Poland. D.Plewczynski@icm.edu.pl
authors.forename: Dariusz
authors.initials: D
authors.lastname: Plewczynski
mesh_terms: D000465:Algorithms; D000991:Antithrombins / Q000737:chemistry; D001499:Bayes Theorem; D003198:Computer Simulation; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry; D003663:Decision Trees; D055808:Drug Discovery / Q000379:methods*; D004965:Estrogen Antagonists / Q000737:chemistry; D005493:Folic Acid Antagonists / Q000737:chemistry; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans; D016014:Linear Models; D008958:Models, Molecular; D016571:Neural Networks, Computer; D025341:Principal Component Analysis; D011506:Proteins / Q000037:antagonists & inhibitors*; D054852:Small Molecule Libraries / Q000737:chemistry*; D060388:Support Vector Machine
chemical_list: D000991:Antithrombins; D052246:Cyclooxygenase 2 Inhibitors; D004965:Estrogen Antagonists; D005493:Folic Acid Antagonists; D011506:Proteins; D054852:Small Molecule Libraries; D054303:HIV Reverse Transcriptase