title: Mining Chemical Activity Status from High-Throughput Screening Assays.
abstract: High-throughput screening (HTS) experiments provide a valuable resource that reports biological activity of numerous chemical compounds relative to their molecular targets. Building computational models that accurately predict such activity status (active vs. inactive) in specific assays is a challenging task given the large volume of data and frequently small proportion of active compounds relative to the inactive ones. We developed a method, DRAMOTE, to predict activity status of chemical compounds in HTP activity assays. For a class of HTP assays, our method achieves considerably better results than the current state-of-the-art-solutions. We achieved this by modification of a minority oversampling technique. To demonstrate that DRAMOTE is performing better than the other methods, we performed a comprehensive comparison analysis with several other methods and evaluated them on data from 11 PubChem assays through 1,350 experiments that involved approximately 500,000 interactions between chemicals and their target proteins. As an example of potential use, we applied DRAMOTE to develop robust models for predicting FDA approved drugs that have high probability to interact with the thyroid stimulating hormone receptor (TSHR) in humans. Our findings are further partially and indirectly supported by 3D docking results and literature information. The results based on approximately 500,000 interactions suggest that DRAMOTE has performed the best and that it can be used for developing robust virtual screening models. The datasets and implementation of all solutions are available as a MATLAB toolbox online at www.cbrc.kaust.edu.sa/dramote and can be found on Figshare.
authors.affiliation: King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Thuwal 23955-6900, Saudi Arabia.
authors.forename: Othman
authors.initials: O
authors.lastname: Soufan
authors.affiliation: King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Thuwal 23955-6900, Saudi Arabia.
authors.forename: Wail
authors.initials: W
authors.lastname: Ba-alawi
authors.affiliation: King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Thuwal 23955-6900, Saudi Arabia.
authors.forename: Moataz
authors.initials: M
authors.lastname: Afeef
authors.affiliation: King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Thuwal 23955-6900, Saudi Arabia.
authors.forename: Magbubah
authors.initials: M
authors.lastname: Essack
authors.affiliation: King Abdullah University of Science and Technology (KAUST), KAUST Catalysis Center (KCC), Thuwal 23955-6900, Saudi Arabia.
authors.forename: Valentin
authors.initials: V
authors.lastname: Rodionov
authors.affiliation: King Abdullah University of Science and Technology (KAUST), Infocloud Group, Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), Thuwal 23955-6900, Saudi Arabia.
authors.forename: Panos
authors.initials: P
authors.lastname: Kalnis
authors.affiliation: King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Thuwal 23955-6900, Saudi Arabia.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Bajic
mesh_terms: D062126:Databases, Chemical; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D011989:Receptors, Thyrotropin / Q000187:drug effects
chemical_list: D011989:Receptors, Thyrotropin