Fan Kunjie, Tang Shan, Gökbağ Birkan, Cheng Lijun, Li Lang
Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States.
College of Pharmacy, The Ohio State University, Columbus, OH, United States.
Front Genet. 2023 Jan 9;13:1103092. doi: 10.3389/fgene.2022.1103092. eCollection 2022.
Synthetic lethal (SL) genetic interactions have been regarded as a promising focus for investigating potential targeted therapeutics to tackle cancer. However, the costly investment of time and labor associated with wet-lab experimental screenings to discover potential SL relationships motivates the development of computational methods. Although graph neural network (GNN) models have performed well in the prediction of SL gene pairs, existing GNN-based models are not designed for predicting cancer cell-specific SL interactions that are more relevant to experimental validation . Besides, neither have existing methods fully utilized diverse graph representations of biological features to improve prediction performance. In this work, we propose MVGCN-iSL, a novel multi-view graph convolutional network (GCN) model to predict cancer cell-specific SL gene pairs, by incorporating five biological graph features and multi-omics data. Max pooling operation is applied to integrate five graph-specific representations obtained from GCN models. Afterwards, a deep neural network (DNN) model serves as the prediction module to predict the SL interactions in individual cancer cells (iSL). Extensive experiments have validated the model's successful integration of the multiple graph features and state-of-the-art performance in the prediction of potential SL gene pairs as well as generalization ability to novel genes.
合成致死(SL)基因相互作用已被视为研究治疗癌症潜在靶向疗法的一个有前景的重点。然而,与通过湿实验室实验筛选来发现潜在的SL关系相关的时间和劳动力成本高昂,这推动了计算方法的发展。尽管图神经网络(GNN)模型在预测SL基因对方面表现出色,但现有的基于GNN的模型并非设计用于预测与实验验证更相关的癌细胞特异性SL相互作用。此外,现有方法都没有充分利用生物特征的多种图表示来提高预测性能。在这项工作中,我们提出了MVGCN-iSL,这是一种新颖的多视图图卷积网络(GCN)模型,通过整合五种生物图特征和多组学数据来预测癌细胞特异性SL基因对。应用最大池化操作来整合从GCN模型获得的五种特定于图的表示。之后,一个深度神经网络(DNN)模型作为预测模块来预测单个癌细胞中的SL相互作用(iSL)。大量实验验证了该模型成功整合了多种图特征,在预测潜在SL基因对方面具有最先进的性能以及对新基因的泛化能力。