title: Towards in silico identification of the human ether-a-go-go-related gene channel blockers: discriminative vs. generative classification models.
abstract: HERG potassium channels have a critical role in the normal electrical activity of the heart. The blockade of hERG channels in heart cells can result in a potentially fatal disorder called long QT syndrome. HERG channels can be blocked by compounds with diverse structures belonging to several drug classes. Presented herein are generative (Generative Topographic Maps) and discriminative (Support Vector Machines) classification models to categorize the compounds in silico into active and inactive classes by using different types of descriptors. The predictive performance of discriminative and generative classification models has been compared. Here, the possibility of using Generative Topographic Maps as an approach for applicability domain analysis and to generate probability-based descriptors was demonstrated to our knowledge for the first time. Comparison of obtained results with the models developed by other teams on the same data set has been performed.
authors.affiliation: Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Moscow, Russia. nkireeva@gmail.com
authors.forename: N
authors.initials: N
authors.lastname: Kireeva
authors.forename: S L
authors.initials: SL
authors.lastname: Kuznetsov
authors.forename: A A
authors.initials: AA
authors.lastname: Bykov
authors.forename: A Yu
authors.initials: AY
authors.lastname: Tsivadze
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D019295:Computational Biology / Q000379:methods; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D015233:Models, Statistical; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000302:isolation & purification*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D026902:Potassium Channel Blockers