Cardiotoxicity Prediction Based on Integreted hERG Database with Molecular Convolution Model

Jieying Hu, Ming Huang, Naoaki Ono, Ye Chen-Izu, Leighton T. Izu, Shigehiko Kanaya

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Cardiotoxicity caused by drug candidates and chemical compounds that block hERG channels may lead to malignant ventricular arrhythmias and even sudden cardiac death (SCD). Various in-silico models have been built to predict the cardiotoxicity during early stages of drug design. The largest public database of hERG-related compounds by integrating several major databases has been constructed recently, which made it possible to build more sophisticated machine learning models for accurate prediction of cardiotoxicity. Here we developed a novel molecular graph convolution neural network (MGCNN) model, based on the new integrated database. The MGCNN models were built by altering the number of graph convolutional layers (GC) from 1 to 5. A random forest (RF) model input with the extended-connectivity fingerprint (ECFP) of different maximal radii (1 ∼ 5) was built to enable a direct comparison with the MCGNN models. We found that the MGCNN model with 2 GCs has the best performance in terms of the ROC-AUC-score (0.84), whereas the RF model input with ECFP has a stable performance (0.77 ∼ 0.80) over the preset radii. The machine learning models promise a potential new approach for harnessing the big data to achieve accurate prediction of drug cardiotoxicity.

Original languageEnglish (US)
Title of host publicationProceedings - 2019 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2019
EditorsIllhoi Yoo, Jinbo Bi, Xiaohua Tony Hu
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages1500-1503
Number of pages4
ISBN (Electronic)9781728118673
DOIs
StatePublished - Nov 2019
Event2019 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2019 - San Diego, United States
Duration: Nov 18 2019Nov 21 2019

Publication series

NameProceedings - 2019 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2019

Conference

Conference2019 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2019
CountryUnited States
CitySan Diego
Period11/18/1911/21/19

Keywords

  • Cardiotoxicity
  • extended-connectivity fingerprint
  • hERG
  • molecular graph convolution neural network

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Molecular Medicine
  • Modeling and Simulation
  • Health Informatics
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health

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  • Cite this

    Hu, J., Huang, M., Ono, N., Chen-Izu, Y., Izu, L. T., & Kanaya, S. (2019). Cardiotoxicity Prediction Based on Integreted hERG Database with Molecular Convolution Model. In I. Yoo, J. Bi, & X. T. Hu (Eds.), Proceedings - 2019 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2019 (pp. 1500-1503). [8983163] (Proceedings - 2019 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2019). Institute of Electrical and Electronics Engineers Inc.. https://doi.org/10.1109/BIBM47256.2019.8983163