title: Supervised extensions of chemography approaches: case studies of chemical liabilities assessment.
abstract: Chemical liabilities, such as adverse effects and toxicity, play a significant role in modern drug discovery process. In silico assessment of chemical liabilities is an important step aimed to reduce costs and animal testing by complementing or replacing in vitro and in vivo experiments. Herein, we propose an approach combining several classification and chemography methods to be able to predict chemical liabilities and to interpret obtained results in the context of impact of structural changes of compounds on their pharmacological profile. To our knowledge for the first time, the supervised extension of Generative Topographic Mapping is proposed as an effective new chemography method. New approach for mapping new data using supervised Isomap without re-building models from the scratch has been proposed. Two approaches for estimation of model's applicability domain are used in our study to our knowledge for the first time in chemoinformatics. The structural alerts responsible for the negative characteristics of pharmacological profile of chemical compounds has been found as a result of model interpretation.
authors.affiliation: Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Leninsky pr-t 31-4, 119071 Moscow, Russia ; Moscow Institute of Physics and Technology, Institutsky per., 9, 141700 Dolgoprudny, Russia.
authors.forename: Svetlana I
authors.initials: SI
authors.lastname: Ovchinnikova
authors.affiliation: Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Leninsky pr-t 31-4, 119071 Moscow, Russia ; Moscow Institute of Physics and Technology, Institutsky per., 9, 141700 Dolgoprudny, Russia.
authors.forename: Arseniy A
authors.initials: AA
authors.lastname: Bykov
authors.affiliation: Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Leninsky pr-t 31-4, 119071 Moscow, Russia.
authors.forename: Aslan Yu
authors.initials: AY
authors.lastname: Tsivadze
authors.affiliation: Kurnakov Institute of General and Inorganic Chemistry RAS, Leninsky pr-t 31, 119071 Moscow, Russia.
authors.forename: Evgeny P
authors.initials: EP
authors.lastname: Dyachkov
authors.affiliation: Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Leninsky pr-t 31-4, 119071 Moscow, Russia ; Moscow Institute of Physics and Technology, Institutsky per., 9, 141700 Dolgoprudny, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Kireeva
keywords: Applicability domain; Cheminformatics; Chemography; Dimensionality reduction; Generative topographic mapping; Isomap; Supervised Isomap; Supervised generative topographic mapping