Expanding gene regulatory networks from transcriptome data through graphical modeling with heterogeneous priors

Abstract

Gene regulatory network inference is widely used to reconstruct large-scale networks and identify functional genes from transcriptome data. Meanwhile, in many biological fields, core regulatory genes have been extensively studied, leading to the establishment of small-scale gene regulatory networks, and novel genes connected to these networks remain to be identified. However, methods for expanding existing gene networks by identifying novel regulatory interactions, rather than reconstructing the entire network, are not well established. Here, we propose a method for gene network expansion that incorporates known regulatory relationships and evaluates each candidate gene individually to infer its regulatory connections to the existing network. Using simulated datasets from the DREAM4 benchmark and the PRECISE-1K experimental dataset, our method outperformed conventional methods by incorporating prior knowledge. In particular, it improved the ability to distinguish true regulatory interactions from indirect associations arising from strong correlations among genes in the existing network. The method also showed strong performance for interactions involving genes with high outdegree or centrality. Furthermore, it maintained stable performance as the size of the existing network increased and was robust to noise in prior information. These results demonstrate that our method provides an effective framework for expanding existing gene regulatory networks by leveraging prior knowledge.