Personalized Driver Gene Prediction Using Graph Convolutional Networks with Conditional Random Fields

Abstract

Cancer is a complex and evolutionary disease mainly driven by the accumulation of genetic variations in genes. Identifying cancer driver genes is important. However, most related studies have focused on the population level. Cancer is a disease with high heterogeneity. Thus, the discovery of driver genes at the individual level is becoming more valuable but is a great challenge. Although there have been some computational methods proposed to tackle this challenge, few can cover all patient samples well, and there is still room for performance improvement. In this study, to identify individual-level driver genes more efficiently, we propose the PDGCN method. PDGCN integrates multiple types of data features, including mutation, expression, methylation, copy number data, and system-level gene features, along with network structural features extracted using Node2vec in order to construct a sample–gene interaction network. Prediction is performed using a graphical convolutional neural network model with a conditional random field layer, which is able to better combine the network structural features with biological attribute features. Experiments on the ACC (Adrenocortical Cancer) and KICH (Kidney Chromophobe) datasets from TCGA (The Cancer Genome Atlas) demonstrated that the method performs better compared to other similar methods. It can identify not only frequently mutated driver genes, but also rare candidate driver genes and novel biomarker genes. The results of the survival and enrichment analyses of these detected genes demonstrate that the method can identify important driver genes at the individual level.

Keywords

• cancer
• driver genes
• multi-omics features
• graph convolutional neural network
• conditional random field layer