Hegde Akshata, Nguyen Tom, Cheng Jianlin
Department of Electrical Engineering and Computer Science, University of Missouri, 416 S 6th St, Columbia, MO 65201, United States.
Roy Blunt Nextgen Precision Health, University of Missouri, 1030 Hitt St, Columbia, MO 65205, United States.
Brief Bioinform. 2025 Aug 31;26(5). doi: 10.1093/bib/bbaf470.
Gene Regulatory Networks (GRNs) are intricate biological systems that control gene expression and regulation in response to environmental and developmental cues. Advances in computational biology, coupled with high-throughput sequencing technologies, have significantly improved the accuracy of GRN inference and modeling. Modern approaches increasingly leverage artificial intelligence (AI), particularly machine learning techniques-including supervised, unsupervised, semi-supervised, and contrastive learning-to analyze large-scale omics data and uncover regulatory gene interactions. To support both the application of GRN inference in studying gene regulation and the development of novel machine learning methods, we present a comprehensive review of machine learning-based GRN inference methodologies, along with the datasets and evaluation metrics commonly used. Special emphasis is placed on the emerging role of cutting-edge deep learning techniques in enhancing inference performance. The major challenges and potential future directions for improving GRN inference are also discussed.