Identification of gene biomarkers for brain diseases via multi-network topological semantics extraction and graph convolutional network

BMC Genomics. 2024 Feb 14;25(1):175. doi: 10.1186/s12864-024-09967-9.

Abstract

Background: Brain diseases pose a significant threat to human health, and various network-based methods have been proposed for identifying gene biomarkers associated with these diseases. However, the brain is a complex system, and extracting topological semantics from different brain networks is necessary yet challenging to identify pathogenic genes for brain diseases.

Results: In this study, we present a multi-network representation learning framework called M-GBBD for the identification of gene biomarker in brain diseases. Specifically, we collected multi-omics data to construct eleven networks from different perspectives. M-GBBD extracts the spatial distributions of features from these networks and iteratively optimizes them using Kullback-Leibler divergence to fuse the networks into a common semantic space that represents the gene network for the brain. Subsequently, a graph consisting of both gene and large-scale disease proximity networks learns representations through graph convolution techniques and predicts whether a gene is associated which brain diseases while providing associated scores. Experimental results demonstrate that M-GBBD outperforms several baseline methods. Furthermore, our analysis supported by bioinformatics revealed CAMP as a significantly associated gene with Alzheimer's disease identified by M-GBBD.

Conclusion: Collectively, M-GBBD provides valuable insights into identifying gene biomarkers for brain diseases and serves as a promising framework for brain networks representation learning.

Keywords: Brain diseases; Gene biomarkers; Gene-disease associations prediction; Graph convolutional network; Multi-network topological semantics.

MeSH terms

  • Alzheimer Disease* / genetics
  • Brain / diagnostic imaging
  • Genetic Markers
  • Humans
  • Learning
  • Semantics*

Substances

  • Genetic Markers