Multi-view learning framework for predicting unknown types of cancer markers via directed graph neural networks fitting regulatory networks.

Journal: Briefings in bioinformatics
Published Date:

Abstract

The discovery of diagnostic and therapeutic biomarkers for complex diseases, especially cancer, has always been a central and long-term challenge in molecular association prediction research, offering promising avenues for advancing the understanding of complex diseases. To this end, researchers have developed various network-based prediction techniques targeting specific molecular associations. However, limitations imposed by reductionism and network representation learning have led existing studies to narrowly focus on high prediction efficiency within single association type, thereby glossing over the discovery of unknown types of associations. Additionally, effectively utilizing network structure to fit the interaction properties of regulatory networks and combining specific case biomarker validations remains an unresolved issue in cancer biomarker prediction methods. To overcome these limitations, we propose a multi-view learning framework, CeRVE, based on directed graph neural networks (DGNN) for predicting unknown type cancer biomarkers. CeRVE effectively extracts and integrates subgraph information through multi-view feature learning. Subsequently, CeRVE utilizes DGNN to simulate the entire regulatory network, propagating node attribute features and extracting various interaction relationships between molecules. Furthermore, CeRVE constructed a comparative analysis matrix of three cancers and adjacent normal tissues through The Cancer Genome Atlas and identified multiple types of potential cancer biomarkers through differential expression analysis of mRNA, microRNA, and long noncoding RNA. Computational testing of multiple types of biomarkers for 72 cancers demonstrates that CeRVE exhibits superior performance in cancer biomarker prediction, providing a powerful tool and insightful approach for AI-assisted disease biomarker discovery.

Authors

  • Xin-Fei Wang
  • Lan Huang
  • Yan Wang
    College of Animal Science and Technology, Beijing University of Agriculture, Beijing, China.
  • Ren-Chu Guan
    Key Laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
  • Zhu-Hong You
    Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China. zhuhongyou@ms.xjb.ac.cn.
  • Nan Sheng
    School of Computer Science and Technology, Heilongjiang University, Harbin 150080, China.
  • Xu-Ping Xie
    Key Laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, No. 2699, Qianjin Street, Changchun 130012, China.
  • Wen-Ju Hou
    Key Laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, No. 2699, Qianjin Street, Changchun, 130012, China.