CancerGATE: Prediction of cancer-driver genes using graph attention autoencoders

Seunghwan Jung, Seunghyun Wang,Doheon Lee

Computers in Biology and Medicine(2024)

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摘要
Discovery of the cancer type specific-driver genes is important for understanding the molecular mechanisms of each cancer type and for providing proper treatment. Recently, graph deep learning methods became widely used in finding cancer-driver genes. However, previous methods had limited performance in individual cancer types due to a small number of cancer-driver genes used in training and biases toward the cancer-driver genes used in training the models. Here, we introduce a novel pipeline, CancerGATE that predicts the cancer-driver genes using graph attention autoencoder(GATE) to learn in a self-supervised manner and can be applied to each of the cancer types. CancerGATE utilizes biological network topology and multi-omics data from 15 types of cancer of 20,079 samples from the cancer genome atlas(TCGA). Attention coefficients calculated in the model are used to prioritize cancer-driver genes by comparing coefficients of cancer and normal contexts. CancerGATE shows a higher AUPRC with a difference ranging from 1.5 % to 36.5 % compared to the previous graph deep learning models in each cancer type. We also show that CancerGATE is free from the bias toward cancer-driver genes used in training, revealing mechanisms of the cancer-driver genes in specific cancer types. Finally, we propose novel cancer-driver gene candidates that could be therapeutic targets for specific cancer types.
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关键词
Cancer-driver gene,Graph convolutional network,Attention mechanism,Multi-omics data,Self-supervised learning,Interpretability
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