title: Beware of Unreliable Q2! A Comparative Study of Regression Metrics for Predictivity Assessment of QSAR Models.
abstract: Validation is an essential step of QSAR modeling, and it can be performed by both internal validation techniques (e.g., cross-validation, bootstrap) or by an external set of test objects, that is, objects not used for model development and/or optimization. The evaluation of model predictive ability is then completed by comparing experimental and predicted values of test molecules. When dealing with quantitative QSAR models, validation results are generally expressed in terms of Q2metrics. In this work, four fundamental mathematical principles, which should be respected by any Q2metric, are introduced. Then, the behavior of five different metrics (QF12, QF22, QF32, QCCC2, and QRm2) is compared and critically discussed. The conclusions highlight that only the QF32metric satisfies all the stated conditions, while the remaining metrics show different theoretical flaws.
authors.affiliation: Milano Chemometrics and QSAR Research Group, Department of Earth and Environmental Sciences, University of Milano-Bicocca , P.za della Scienza, 1, 20126 Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Todeschini
authors.affiliation: Milano Chemometrics and QSAR Research Group, Department of Earth and Environmental Sciences, University of Milano-Bicocca , P.za della Scienza, 1, 20126 Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Ballabio
authors.affiliation: Milano Chemometrics and QSAR Research Group, Department of Earth and Environmental Sciences, University of Milano-Bicocca , P.za della Scienza, 1, 20126 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Grisoni
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship