Network-based protein-protein interaction prediction method maps perturbations of cancer interactome

Qiu, Jiajun; Chen, Kui; Zhong, Chunlong; Zhu, Sihao; Ma, Xiao

The perturbations of protein-protein interactions (PPIs) were found to be the main cause of cancer. Previous gene relationship prediction methods which were trained with non-disease gene interaction data were not compatible to map the PPI network in cancer. Therefore, we established a novel cancer specific PPI prediction method dubbed NECARE, which was based on relational graph convolutional network (R-GCN) with knowledge-based features. It achieved the best performance with a Matthews correlation coefficient (MCC) = 0.84±0.03 and an F1 = 91±2% comparing with other methods. With NECARE, we mapped the cancer interactome atlas and revealed that the perturbations of PPIs were enriched on 1362 genes, which were named cancer hub genes. Those genes were found to over-represent with mutations occurring at protein-macromolecules binding interfaces. Furthermore, over 42% of cancer treatment-related genes belonged to hub genes, which were significantly related to the prognosis of 32 types of cancers. Finally, by coimmunoprecipitation, we confirmed that the NECARE prediction method was highly reliable with a 90% accuracy. Overall, we provided the novel network-based protein-protein interaction prediction method and mapped the perturbation of cancer interactome. NECARE is available at: https://github.com/JiajunQiu/NECARE.