MiRGraph: A hybrid deep learning approach to identify microRNA-target interactions by integrating heterogeneous regulatory network and genomic sequences

Pei Liu, Ying Liu, Jiawei Luo, Yue Li

Abstract: MicroRNAs (miRNAs) mediates gene expression regulation by targeting specific messenger RNAs (mRNAs) in the cytoplasm. They can function as both tumor suppressors and oncogenes depending on the specific miRNA and its target genes. Detecting miRNA-target interactions (MTIs) is critical for unraveling the complex mechanisms of gene regulation and promising towards RNA therapy for cancer. There is currently a lack of MTIs prediction methods that simultaneously perform feature learning from heterogeneous gene regulatory network (GRN) and genomic sequences. To improve the prediction performance of MTIs, we present a novel transformer-based multi-view feature learning method – MiRGraph, which consists of two main modules for learning the sequence-based and GRN-based feature embedding. For the former, we utilize the mature miRNA sequences and the complete 3'UTR sequence of the target mRNAs to encode sequence features using a hybrid transformer and convolutional neural network (CNN) (TransCNN) architecture. For the latter, we utilize a heterogeneous graph transformer (HGT) module to extract the relational and structural information from the GRN consisting of miRNA-miRNA, gene-gene and miRNA-target interactions. The TransCNN and HGT modules can be learned end-to-end to predict experimentally validated MTIs from MiRTarBase. MiRGraph outperforms existing methods in not only recapitulating the true MTIs but also in predicting strength of the MTIs based on the in-vitro measurements of miRNA transfections. In a case study on breast cancer, we identified plausible target genes of an oncomir.