Hierarchical graph transformer with contrastive learning for gene regulatory network inference.

Abstract

Gene regulatory networks (GRNs) are crucial for understanding gene regulation and cellular processes. Inferring GRNs helps uncover regulatory pathways, shedding light on the regulation and development of cellular processes. With the rise of high-throughput sequencing and advancements in computational technology, computational models have emerged as cost-effective alternatives to traditional experimental studies. Moreover, the surge in ChIPseq data for TF-DNA binding has catalyzed the development of graph neural network (GNN)-based methods, greatly advancing GRN inference capabilities. However, most existing GNN-based methods suffer from the inability to capture long-distance structural semantic correlations due to transitive interactions. In this paper, we introduce a novel GNN-based model named Hierarchical Graph Transformer with Contrastive Learning for GRN (HGTCGRN) inference. HGTCGRN excels at capturing structural semantics using a hierarchical graph Transformer, which introduces a series of gene family nodes representing gene functions as virtual nodes to interact with nodes in the GRNS. These semanticaware virtual-node embeddings are aggregated to produce node representations with varying emphasis. Additionally, we leverage gene ontology information to construct gene interaction networks for contrastive learning optimization of GRNs. Experimental results demonstrate that HGTCGRN achieves superior performance in GRN inference.