InfoSEM: A Deep Generative Model with Informative Priors for Gene Regulatory Network Inference

Inferring Gene Regulatory Networks (GRNs) from gene expression data is crucial for understanding biological processes. While supervised models are reported to achieve high performance for this task, they rely on costly ground truth (GT) labels and risk learning gene-specific biases—such as class imbalances of GT interactions—rather than true regulatory mechanisms. To address these issues, we introduce InfoSEM, an unsupervised generative model that leverages textual gene embeddings as informative priors, improving GRN inference without GT labels. InfoSEM can also integrate GT labels as an additional prior when available, avoiding biases and further enhancing performance. Additionally, we propose a biologically motivated benchmarking framework that better reflects real-world applications such as biomarker discovery and reveals learned biases of existing supervised methods. InfoSEM outperforms existing models by 38.5% across four datasets using textual embeddings prior and further boosts performance by 11.1% when integrating labeled data as priors.