融合多组学与蛋白网络图卷积,精准预测达拉非尼抗癌药敏感性。
Modeling Dabrafenib Response Using Multi-Omics Modality Fusion and Protein Network Embeddings Based on Graph Convolutional Networks
- 用图卷积网络融合蛋白互作信息,生成多组学低维表示。
- 仅整合蛋白组与转录组数据时预测准确率最高(R²≈0.96)。
- 适用于精准肿瘤学中靶向药物响应的计算建模研究。
靶向治疗在癌细胞中的反应源于复杂的分子互作,单一组学难以准确预测。本研究构建模型,通过整合基因组、转录组、蛋白组、表观遗传组和代谢组五层数据,并利用图卷积网络(GCN)生成蛋白互作网络嵌入,以捕捉生物学拓扑结构。每类数据经神经网络预处理为低维表示,再通过注意力机制自适应分配权重。基于GDSC癌细胞系数据,发现仅融合蛋白组与转录组数据时表现最优(测试R²约0.96),优于单一组学及全模态组合。基因组与表观遗传数据信息量较低,而蛋白组与转录组提供了与MAPK抑制剂活性更强相关的表型信号。结果表明,注意力引导的多组学融合结合GCN可显著提升药物响应预测能力,并揭示达拉非尼敏感性的互补分子决定因素,为精准肿瘤学与靶向治疗预测建模提供有效计算框架。
原文摘要 · Abstract (English)
Cancer cell response to targeted therapy arises from complex molecular interactions, making single omics insufficient for accurate prediction. This study develops a model to predict Dabrafenib sensitivity by integrating multiple omics layers (genomics, transcriptomics, proteomics, epigenomics, and metabolomics) with protein network embeddings generated using Graph Convolutional Networks (GCN). Each modality is encoded into low dimensional representations through neural network preprocessing. Protein interaction information from STRING is incorporated using GCN to capture biological topology. An attention based fusion mechanism assigns adaptive weights to each modality according to its relevance. Using GDSC cancer cell line data, the model shows that selective integration of two modalities, especially proteomics and transcriptomics, achieves the best test performance (R2 around 0.96), outperforming all single omics and full multimodal settings. Genomic and epigenomic data were less informative, while proteomic and transcriptomic layers provided stronger phenotypic signals related to MAPK inhibitor activity. These results show that attention guided multi omics fusion combined with GCN improves drug response prediction and reveals complementary molecular determinants of Dabrafenib sensitivity. The approach offers a promising computational framework for precision oncology and predictive modeling of targeted therapies.
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