AUTHOR=Wang Shuran , Zhang Lilian , Gao Lutao , Rao Yao , Cui Jie , Yang Linnan 

TITLE=GTAT-GRN: a graph topology-aware attention method with multi-source feature fusion for gene regulatory network inference

JOURNAL=Frontiers in Genetics

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2025.1668773

DOI=10.3389/fgene.2025.1668773

ISSN=1664-8021

ABSTRACT=Gene regulatory network (GRN) inference is a central task in systems biology. However, due to the noisy nature of gene expression data and the diversity of regulatory structures, accurate GRN inference remains challenging. We hypothesize that integrating multi-source features and leveraging an attention mechanism that explicitly captures graph structure can enhance GRN inference performance. Based on this, we propose GTAT-GRN, a deep graph neural network model with a graph topological attention mechanism that fuses multi-source features. GTAT-GRN includes a feature fusion module to jointly model temporal expression patterns, baseline expression levels, and structural topological attributes, improving node representation. In addition, we introduce the Graph Topology-Aware Attention Network (GTAT), which combines graph structure information with multi-head attention to capture potential gene regulatory dependencies. We conducted comprehensive evaluations of GTAT-GRN on multiple benchmark datasets and compared it with several state-of-the-art inference methods, including GENIE3 and GreyNet. The experimental results show that GTAT-GRN consistently achieves higher inference accuracy and improved robustness across datasets. These findings indicate that integrating graph topological attention with multi-source feature fusion can effectively enhance GRN reconstruction.