Conformal prediction of HDAC inhibitors

ABSTRACTThe growing interest in epigenetic probes and drug discovery, as revealed by several epigenetic drugs in clinical use or in the lineup of the drug development pipeline, is boosting the generation of screening data. In order to maximize the use of structure–activity relationships there is a clear need to develop robust and accurate models to understand the underlying structure–activity relationship. Similarly, accurate models should be able to guide the rational screening of compound libraries. Herein we introduce a novel approach for epigenetic quantitative structure–activity relationship (QSAR) modelling using conformal prediction. As a case study, we discuss the development of models for 11 sets of inhibitors of histone deacetylases (HDACs), which are one of the major epigenetic target families that have been screened. It was found that all derived models, for every HDAC endpoint and all three significance levels, are valid with respect to predictions for the external test sets as well as the in...