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DriverOmicsNet:用于癌症驱动基因多组学探索的集成图卷积网络

DriverOmicsNet: an integrated graph convolutional network for multi-omics exploration of cancer driver genes.

作者信息

Dai Yang-Hong, Chang Chia-Jun, Shen Po-Chien, Jheng Wun-Long, Lee Ding-Jie, Chen Yu-Guang

机构信息

Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical University, No. 325, Sec. 2, Chenggong Rd., Neihu District, Taipei City 114202, Taiwan, Republic of China.

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, United Kingdom.

出版信息

Brief Bioinform. 2025 Jul 2;26(4). doi: 10.1093/bib/bbaf412.

Abstract

Cancer is a complex and heterogeneous group of diseases driven by genetic mutations and molecular changes. Identifying and characterizing cancer driver gene is crucial for understanding cancer biology and guiding precision oncology. Integrating multi-omics data can reveal the intricate molecular interactions underlying cancer progression and treatment responses. We developed a graph convolutional network (GCN) framework, DriverOmicsNet, that integrates multi-omics data using STRING protein-protein interaction networks and correlation-based weighted gene correlation network analysis (WGCNA). We applied this framework to 15 cancer types, analyzing 5555 tumor samples to predict cancer-related features such as homologous recombination deficiency, cancer stemness, immune clusters, tumor stage, and survival outcomes. DriverOmicsNet demonstrated superior predictive accuracy and model performance metrics across all target labels when compared with GCN models based on STRING network alone. Gene expression emerged as the most significant feature, reflecting the dynamic and functional state of cancer cells. The combined use of STRING PPI and WGCNA networks enhanced the identification of key driver genes and their interactions. Our study highlights the effectiveness of using GCNs to integrate multi-omics data for precision oncology. The integration of STRING PPI and WGCNA networks provides a comprehensive framework that improves predictive power and facilitates the understanding of cancer biology, paving the way for more tailored treatments.

摘要

癌症是一组由基因突变和分子变化驱动的复杂且异质性的疾病。识别和表征癌症驱动基因对于理解癌症生物学和指导精准肿瘤学至关重要。整合多组学数据可以揭示癌症进展和治疗反应背后复杂的分子相互作用。我们开发了一种图卷积网络(GCN)框架DriverOmicsNet,它使用STRING蛋白质-蛋白质相互作用网络和基于相关性的加权基因共表达网络分析(WGCNA)来整合多组学数据。我们将此框架应用于15种癌症类型,分析了5555个肿瘤样本,以预测癌症相关特征,如同源重组缺陷、癌症干性、免疫簇、肿瘤分期和生存结果。与仅基于STRING网络的GCN模型相比,DriverOmicsNet在所有目标标签上都表现出卓越的预测准确性和模型性能指标。基因表达成为最显著的特征,反映了癌细胞的动态和功能状态。STRING PPI和WGCNA网络的联合使用增强了关键驱动基因及其相互作用的识别。我们的研究强调了使用GCN整合多组学数据用于精准肿瘤学的有效性。STRING PPI和WGCNA网络的整合提供了一个全面的框架,提高了预测能力并促进了对癌症生物学的理解,为更个性化的治疗铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f393/12354958/e8a595c92ebc/bbaf412f1.jpg

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