DMDGRN: A data augmentation-based multilayer directed graph convolutional network for gene regulatory network inference.

OBJECTIVE

Gene regulatory networks (GRNs) provide a graphical representation of the regulatory interactions between transcription factors (TFs) and their target genes, governing transcriptional states that define cell identity and function. Deciphering GRNs is fundamental for deciphering disease pathogenesis and remains a central challenge in systems biology. Graph neural network-based methods have made significant progress in GRN inference in recent years due to their exceptional ability to model graph-structured biological data. However, the inherent characteristics of GRNs usually have been ignored, including the directionality, the sparsity and abundant high-order regulatory interactions of GRNs.

METHODS

In this study, we propose DMDGRN, a data augmentation-based multilayer directed graph convolutional network for GRN inference. To capture the direction of GRNs, DMDGRN employs phase matrix to construct the Laplacian operator, which can track message propagation pathways. Considering the inherent sparsity of known GRNs, DMDGRN incorporates data augmentation techniques to overcome the network sparsity. Moreover, DMDGRN adopts a multilayer directed network architecture with residual connections to extract higher-order neighborhood information.

RESULTS

Comprehensive evaluations on benchmark datasets demonstrate that DMDGRN significantly improves GRN inference accuracy. Notably, the application on breast cancer shows that our framework successfully identifies relevant therapeutic candidates for human breast cancer.

CONCLUSIONS

The findings demonstrate that the strategies we adopted are effective for inferring GRNs. The successful application to breast cancer data further highlights its potential of DMDGRN in uncovering disease-relevant regulatory mechanisms and identifying therapeutic targets, making it a promising tool for advancing both computational biology and translational medicine.