TRAPT: a multi-stage fused deep learning framework for predicting transcriptional regulators based on large-scale epigenomic data.

Journal: Nature communications
PMID:

Abstract

It is challenging to identify regulatory transcriptional regulators (TRs), which control gene expression via regulatory elements and epigenomic signals, in context-specific studies on the onset and progression of diseases. The use of large-scale multi-omics epigenomic data enables the representation of the complex epigenomic patterns of control of the regulatory elements and the regulators. Herein, we propose Transcription Regulator Activity Prediction Tool (TRAPT), a multi-modality deep learning framework, which infers regulator activity by learning and integrating the regulatory potentials of target gene cis-regulatory elements and genome-wide binding sites. The results of experiments on 570 TR-related datasets show that TRAPT outperformed state-of-the-art methods in predicting the TRs, especially in terms of forecasting transcription co-factors and chromatin regulators. Moreover, we successfully identify key TRs associated with diseases, genetic variations, cell-fate decisions, and tissues. Our method provides an innovative perspective on identifying TRs by using epigenomic data.

Authors

  • Guorui Zhang
    Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.
  • Chao Song
    Medical School of Chinese PLA, 100853 Beijing, China.
  • Mingxue Yin
    The First Affiliated Hospital & National Health Commission Key Laboratory of Birth Defect Research and Prevention, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
  • Liyuan Liu
    State Key Laboratory of Superlattices and Microstructures, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083, China.
  • Yuexin Zhang
    School of Business Administration, Guizhou University of Finance and Economics, Guiyang, Guizhou, 550025, The People's Republic of China. xin225522@qq.com.
  • Ye Li
    Environment and Plant Protection Institute, Chinese Academy of Tropical Agricultural Science, Haikou 571010, People's Republic of China; Key Laboratory of Monitoring and Control of Tropical Agricultural and Forest Invasive Alien Pests, Ministry of Agriculture, Haikou 571010, People's Republic of China.
  • Jianing Zhang
    Faculty of Psychology, Tianjin Normal University, Tianjin, China.
  • Maozu Guo
    School of Computer Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, China.
  • Chunquan Li