Systematic Functional Annotation and Visualization of Biological Networks
Systematic Functional Annotation and Visualization of Biological Networks
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DOI：
10.1016/j.cels.2016.04.014
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发表时间：
2016-06-22
期刊：
影响因子：
9.3
通讯作者：
Baryshnikova, Anastasia
中科院分区：
文献类型：
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作者：
Baryshnikova, Anastasia
大规模的生物网络代表了基因之间的关系，但我们对网络如何在功能上组织的理解是有限的。在这里，我描述的空间分析功能富集（SAFE），注释生物网络和检查其功能组织的系统方法。SAFE在2D空间中可视化网络，并测量局部社区中功能富集的连续分布，生成相关功能的列表及其相对位置的地图。我应用SAFE对酿酒酵母遗传相互作用相似性网络和蛋白质-蛋白质相互作用网络进行了基因本体论的标注。遗传网络的SAFE注释与手动导出的注释相匹配，而花费的时间不到1%，并且证明对噪声具有鲁棒性，对生物信号敏感。使用SAFE整合遗传相互作用和化学基因组学数据，揭示了囊泡介导的转运与抗癌药物硼替佐米耐药性之间的联系。这些结果证明了SAFE用于检查生物网络和理解其功能组织的实用性。
Large-scale biological networks represent relationships between genes, but our understanding of how networks are functionally organized is limited. Here, I describe spatial analysis of functional enrichment (SAFE), a systematic method for annotating biological networks and examining their functional organization. SAFE visualizes the network in 2D space and measures the continuous distribution of functional enrichment across local neighborhoods, producing a list of the associated functions and a map of their relative positioning. I applied SAFE to annotate the Saccharomyces cerevisiae genetic interaction similarity network and protein-protein interaction network with gene ontology terms. SAFE annotations of the genetic network matched manually derived annotations, while taking less than 1% of the time, and proved robust to noise and sensitive to biological signal. Integration of genetic interaction and chemical genomics data using SAFE revealed a link between vesicle-mediate transport and resistance to the anti-cancer drug bortezomib. These results demonstrate the utility of SAFE for examining biological networks and understanding their functional organization.