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

**Authors:** Shuran Wang, Lilian Zhang, Lutao Gao, Yao Rao, Jie Cui, Linnan Yang

PMC · DOI: 10.3389/fgene.2025.1668773 · Frontiers in Genetics · 2025-10-08

## TL;DR

This paper introduces GTAT-GRN, a new method for predicting gene regulatory networks by combining graph structure and multi-source data.

## Contribution

The novel approach integrates graph topology-aware attention with multi-source feature fusion to improve GRN inference.

## Key findings

- GTAT-GRN outperforms existing methods like GENIE3 and GreyNet in GRN inference accuracy.
- The model shows improved robustness across multiple benchmark datasets.
- Combining graph structure with multi-source features enhances gene regulatory network reconstruction.

## 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.

## Full-text entities

- **Diseases:** cancer (MESH:D009369), tumorigenesis (MESH:D063646)
- **Species:** Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Escherichia coli (E. coli, species) [taxon 562]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12540167/full.md

## References

63 references — full list in the complete paper: https://tomesphere.com/paper/PMC12540167/full.md

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Source: https://tomesphere.com/paper/PMC12540167