KINDLE: Knowledge-Guided Distillation for Prior-Free Gene Regulatory Network Inference

Gene regulatory network (GRN) inference serves as a cornerstone for deciphering cellular decision-making processes. Early approaches rely exclusively on gene expression data, thus their predictive power remain fundamentally constrained by the vast combinatorial space of potential gene-gene interactions. Subsequent methods integrate prior knowledge to mitigate this challenge by restricting the solution space to biologically plausible interactions. However, we argue that the effectiveness of these approaches is contingent upon the precision of prior information and the reduction in the search space will circumscribe the models' potential for novel biological discoveries. To address these limitations, we introduce KINDLE, a three-stage framework that decouples GRN inference from prior knowledge dependencies.