论文标题

生物网络的超图模型鉴定对致病病毒反应至关重要的基因

Hypergraph Models of Biological Networks to Identify Genes Critical to Pathogenic Viral Response

论文作者

Feng, Song, Heath, Emily, Jefferson, Brett, Joslyn, Cliff, Kvinge, Henry, Mitchell, Hugh D., Praggastis, Brenda, Eisfeld, Amie J., Sims, Amy C., Thackray, Larissa B., Fan, Shufang, Walters, Kevin B., Halfmann, Peter J., Westhoff-Smith, Danielle, Tan, Qing, Menachery, Vineet D., Sheahan, Timothy P., Cockrell, Adam S., Kocher, Jacob F., Stratton, Kelly G., Heller, Natalie C., Bramer, Lisa M., Diamond, Michael S., Baric, Ralph S., Waters, Katrina M., Kawaoka, Yoshihiro, McDermott, Jason E., Purvine, Emilie

论文摘要

背景:将生物网络表示为图形是一种有力的方法,可以从高通量生物分子数据中揭示潜在的模式,签名和关键组件。但是,图并未本质地捕获生物系统中基因和蛋白质之间存在的多路关系。超图是图形的概括,它们自然地模拟了多路关系,并在建模系统(例如蛋白质复合物和代谢反应)中显示了希望。在本文中,我们试图了解超图如何基于基于基因组表达数据集推断的复杂关系而更忠实地识别并有潜在地预测重要基因。 结果:我们编制了一个新型的转录宿主对病毒病毒感染反应的数据集,并在基因之间作为超颗粒之间的配制关系,其中超蛋白质代表了受扰动的基因,而顶点代表具有特定实验条件的个体生物样品。我们发现,与图中心性相比,高颗粒中间性中心性是鉴定对病毒反应重要的基因的出色方法。 结论:我们的结果表明,使用超图代表复杂的生物系统并突出了各种高度致病病毒的共同点的中心重要反应的实用性。

Background: Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions. In this paper we seek to understand how hypergraphs can more faithfully identify, and potentially predict, important genes based on complex relationships inferred from genomic expression data sets. Results: We compiled a novel data set of transcriptional host response to pathogenic viral infections and formulated relationships between genes as a hypergraph where hyperedges represent significantly perturbed genes, and vertices represent individual biological samples with specific experimental conditions. We find that hypergraph betweenness centrality is a superior method for identification of genes important to viral response when compared with graph centrality. Conclusions: Our results demonstrate the utility of using hypergraphs to represent complex biological systems and highlight central important responses in common to a variety of highly pathogenic viruses.

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