title: Modeling Choices for Virtual Screening Hit Identification.
abstract: Making suitable modeling choices is crucial for successful in silico drug design, and one of the most important of these is the proper extraction and curation of data from qHTS screens, and the use of optimized statistical learning methods to obtain valid models. More specifically, we aim to learn the top-1 % most potent compounds against a variety of targets in a procedure we call virtual screening hit identification (VISHID). To do so, we exploit quantitative high-throughput screens (qHTS) obtained from PubChem, descriptors derived from molecular structures, and support vector machines (SVM) for model generation. Our results illustrate how an appreciation of subtle issues underlying qHTS data extraction and the resulting SVM models created using these data can enhance the effectiveness of solutions and, in doing so, accelerate drug discovery.
authors.affiliation: Department of Mathematical Sciences, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York, 12180 phone/fax: (518) 276-6414, (518) 276-4824. chbergeron@gmail.com, bergec@rpi.edu.|Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York, 12180. chbergeron@gmail.com, bergec@rpi.edu.|Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, 261 Mountain View Drive, Colchester, Vermont, 05446. chbergeron@gmail.com, bergec@rpi.edu.
authors.forename: Charles
authors.initials: C
authors.lastname: Bergeron
authors.affiliation: Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York, 12180.
authors.forename: Michael
authors.initials: M
authors.lastname: Krein
authors.affiliation: Department of Mathematical Sciences, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York, 12180 phone/fax: (518) 276-6414, (518) 276-4824.|Syracuse North Campus, Bryant and Stratton College, 8687 Carling Road, Syracuse, New York, 13090.
authors.forename: Gregory
authors.initials: G
authors.lastname: Moore
authors.affiliation: Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York, 12180.
authors.forename: Curt M
authors.initials: CM
authors.lastname: Breneman
authors.affiliation: Department of Mathematical Sciences, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York, 12180 phone/fax: (518) 276-6414, (518) 276-4824.
authors.forename: Kristin P
authors.initials: KP
authors.lastname: Bennett
keywords: Balanced classification; Computational chemistry; Drug design; Fast algorithms; High-throughput screening; Kernel functions; Molecular descriptors; Screening hit identification; Support vector machines