Machine learning methods for gene regulatory network inference

Akshata Hegde, Tom Nguyen, Jianlin Cheng

Abstract: 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.