Identifying cancer driver genes based on multi-view heterogeneous graph convolutional network and self-attention...

Correctly identifying the driver genes that promote cell growth can significantly assist drug design, cancer diagnosis and treatment. The recent large-scale cancer genomics projects have revealed multi-omics data from thousands of cancer patients, which requires to design effective models to unlock the hidden knowledge within the valuable data and discover cancer drivers contributing to tumorigenesis.

In this work, we propose a graph convolution network-based method called MRNGCN that integrates multiple gene relationship networks to identify cancer driver genes. First, we constructed three gene relationship networks, including the gene-gene, gene-outlying gene and gene-miRNA networks. Then, genes learnt feature presentations from the three networks through three sharing-parameter heterogeneous graph convolution network (HGCN) models with the self-attention mechanism. After that, these gene features pass a convolution layer to generate fused features. Finally, we utilized the fused features and the original feature to optimize the model by minimizing the node and link prediction losses. Meanwhile, we combined the fused features, the original features and the three features learned from every network through a logistic regression model to predict cancer driver genes.

We applied the MRNGCN to predict pan-cancer and cancer type-specific driver genes. Experimental results show that our model performs well in terms of the area under the ROC curve (AUC) and the area under the precision-recall curve (AUPRC) compared to state-of-the-art methods. Ablation experimental results show that our model successfully improved the cancer driver identification by integrating multiple gene relationship networks.