Epigenetic target identification strategy based on multi-feature learning.

Journal: Journal of biomolecular structure & dynamics
PMID:

Abstract

The identification of potential epigenetic targets for a known bioactive compound is essential and promising as more and more epigenetic drugs are used in cancer clinical treatment and the availability of chemogenomic data related to epigenetics increases. In this study, we introduce a novel epigenetic target identification strategy (ETI-Strategy) that integrates a multi-task graph convolutional neural network prior model and a protein-ligand interaction classification discriminating model using large-scale bioactivity data for a panel of 55 epigenetic targets. Our approach utilizes machine learning techniques to achieve an AUC value of 0.934 for the prior model and 0.830 for the discriminating model, outperforming inverse docking in predicting protein-ligand interactions. When comparing with other open-source target identification tools, it was found that only our tool was able to accurately predict all the targets corresponding to each compound. This further demonstrates the ability of our strategy to take full advantage of molecular-level information as well as protein-level information in molecular activity prediction. Our work highlights the contribution of machine learning in the identification of potential epigenetic targets and offers a novel approach for epigenetic drug discovery and development.Communicated by Ramaswamy H. Sarma.

Authors

  • Lingfeng Chen
    Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China.
  • Rui Gu
    Ethnic Medical School, Chengdu University of Traditional Chinese Medicine, Chengdu 611131, China.
  • Yuanyuan Li
    Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Haichun Liu
    Laboratory of Molecular Design and Drug Discovery, School of Science, China; Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198 Jiangsu, China.
  • Weijie Han
    Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, Nanjing, China.
  • YingChao Yan
    Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China.
  • Yadong Chen
    Laboratory of Molecular Design and Drug Discovery, School of Science, China; Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198 Jiangsu, China.
  • Yanmin Zhang
    Department of Paediatric Cardiology, Shaanxi Institute for Pediatric Diseases, Affiliate Children's Hospital of Xi'an Jiaotong University, Xi'an, China.
  • Yulei Jiang
    From the Department of Radiology, University of Chicago, 5841 S Maryland Ave, MC2026, Chicago, IL 60637.