title: QSAR model as a random event: A case of rat toxicity.
abstract: Quantitative structure-property/activity relationships (QSPRs/QSARs) can be used to predict physicochemical and/or biochemical behavior of substances which were not studied experimentally. Typically predicted values for chemicals in the training set are accurate since they were used to build the model. QSPR/QSAR models must be validated before they are used in practice. Unfortunately, the majority of the suggested approaches of the validation of QSPR/QSAR models are based on consideration of geometrical features of clusters of data points in the plot of experimental versus calculated values of an endpoint. We believe these geometrical criteria can be more useful if they are analyzed for several splits into the training and test sets. In this way, one can estimate the reproducibility of the model with various splits and better evaluate model reliability. The probability of the correct prediction of an endpoint for external validation set (in the series of the above-mentioned splits) can provide an useful way to evaluate the domain of applicability of the model.
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156, Via La Masa 19, Milano, Italy.
authors.forename: Alla P
authors.initials: AP
authors.lastname: Toropova
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156, Via La Masa 19, Milano, Italy. Electronic address: andrey.toropov@marionegri.it.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Toropov
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156, Via La Masa 19, Milano, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Benfenati
authors.affiliation: Interdisciplinary Nanotoxicity Center, Department of Civil and Environmental Engineering, Jackson State University, 1325 Lynch St, Jackson, MS 39217-0510, USA.
authors.forename: Danuta
authors.initials: D
authors.lastname: Leszczynska
authors.affiliation: Interdisciplinary Nanotoxicity Center, Department of Chemistry and Biochemistry, Jackson State University, 1400 J.R. Lynch Street, PO Box 17910, Jackson, MS 39217, USA.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Leszczynski
mesh_terms: D000818:Animals; D007928:Lethal Dose 50; D008958:Models, Molecular; D009930:Organic Chemicals / Q000737:chemistry / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D015203:Reproducibility of Results; D012984:Software
chemical_list: D009930:Organic Chemicals
keywords: CORAL software; Domain of applicability; Oral rat toxicity; QSAR; Validation