Integral Sign Change Problem Check in Quantitative Structure-Activity/Property Relationships: A Tutorial

Abstract

Abstract. Sign change problem (SCP) in multivariate Quantitative Structure-Activity/Property Relationships (QSAR/QSPR) is the inconsistency in the direction of association between molecular descriptors and the dependent variable. Sign change is observed when the signs of the elements of the reference vector (correlation vector for the data set obtained from variable selection) are compared to the signs of the elements of all correlation and regression vectors related to a model. SCP check in this work, named Integral SCP (ISCP) check, is established to be a general effective anti-SCP procedure, consisting of five check levels. Twelve diverse QSAR/QSPR data sets from literature were tested, and performance of data sets, models and descriptors was assessed by qualitative labeling systems. Most data sets and models did not have satisfactory performance, what is discussed in terms possible data and model remedy.