A self-attention-driven deep learning framework for inference of transcriptional gene regulatory networks.

Journal: Briefings in bioinformatics
Published Date:

Abstract

The interactions between transcription factors (TFs) and the target genes could provide a basis for constructing gene regulatory networks (GRNs) for mechanistic understanding of various biological complex processes. From gene expression data, particularly single-cell transcriptomic data containing rich cell-to-cell variations, it is highly desirable to infer TF-gene interactions (TGIs) using deep learning technologies. Numerous models or software including deep learning-based algorithms have been designed to identify transcriptional regulatory relationships between TFs and the downstream genes. However, these methods do not significantly improve predictions of TGIs due to some limitations regarding constructing underlying interactive structures linking regulatory components. In this study, we introduce a deep learning framework, DeepTGI, that encodes gene expression profiles from single-cell and/or bulk transcriptomic data and predicts TGIs with high accuracy. Our approach could fuse the features extracted from Auto-encoder with self-attention mechanism and other networks and could transform multihead attention modules to define representative features. By comparing it with other models or methods, DeepTGI exhibits its superiority to identify more potential TGIs and to reconstruct the GRNs and, therefore, could provide broader perspectives for discovery of more biological meaningful TGIs and for understanding transcriptional gene regulatory mechanisms.

Authors

  • Yong Liu
    Department of Critical care medicine, Shenzhen Hospital, Southern Medical University, Guangdong, Shenzhen, China.
  • Le Zhong
    College of Electronic Information, Guangxi Minzu University, 188 East University Road, Nanning, Guangxi, 530006, China.
  • Bin Yan
    National Digital Switching System Engineering and Technological Research Centre, Zhengzhou, China.
  • Zhuobin Chen
    School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 66 Gongchang Road, Shenzhen, Guangdong, 518107, China.
  • Yanjia Yu
    College of Electronic Information, Guangxi Minzu University, 188 East University Road, Nanning, Guangxi, 530006, China.
  • Dan Yu
    Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, Hangzhou, 310003, People's Republic of China.
  • Jing Qin
    School of Nursing, The Hong Kong Polytechnic University, Hong Kong, China.
  • Junwen Wang
    Department of Health Sciences Research and Center for Individualized Medicine, Mayo Clinic, Scottsdale, Arizona, USAWang.Junwen@mayo.edu.