Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks.
Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks.
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系统的调查揭示了基因共表达网络中“逐罪”的一般适用性。
DOI：
10.1186/1471-2105-6-227
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发表时间：
2005-09-14
影响因子：
3
通讯作者：
Butte AJ
中科院分区：
文献类型：
--
作者：
Wolfe CJ;Kohane IS;Butte AJ
生物过程是由相互作用的分子的协调模块进行的。由于聚类方法表明，表达相似的基因显示出与共同功能模块相关的可能性增加，共表达基因网络为分配基因功能提供了一个框架。这就形成了关联内疚(GBA)启发式，在功能基因组学中被广泛引用。然而，尽管GBA的想法被接受，但GBA的适用范围尚不确定。我们开发了一些方法来系统地探索GBA在大量和不同的表达数据语料库中的广度，以回答以下问题：GBA启发式在多大程度上广泛适用于转录组，相反，GBA在多大程度上被基因本体论(GO)中代表的先验知识捕获？我们的研究使用来自三个哺乳动物生物体的数据对五个共表达网络的功能组织进行了调查。我们的方法计算每个基因和每个基因本体类别之间的概率分数，反映GO模块的共表达丰富。对于每个围棋类别，我们使用接收器操作曲线来评估这些概率分数是否反映了GBA。这一方法应用于五个不同的共表达网络，表明关联内疚的签名是普遍存在和可重现的，并且GBA启发式方法广泛适用于900个基因本体类别的人群。我们还证明了一些GO类别之间存在高度可重复性的共表达模式。我们得出结论，GBA具有普遍价值，转录控制可能比以前实现的更加模块化。我们的分析还表明，在生物定义的模块中组合跨多个基因的共表达测量的方法可以帮助表征基因功能或表征功能对是否一起工作。
Biological processes are carried out by coordinated modules of interacting molecules. As clustering methods demonstrate that genes with similar expression display increased likelihood of being associated with a common functional module, networks of coexpressed genes provide one framework for assigning gene function. This has informed the guilt-by-association (GBA) heuristic, widely invoked in functional genomics. Yet although the idea of GBA is accepted, the breadth of GBA applicability is uncertain. We developed methods to systematically explore the breadth of GBA across a large and varied corpus of expression data to answer the following question: To what extent is the GBA heuristic broadly applicable to the transcriptome and conversely how broadly is GBA captured by a priori knowledge represented in the Gene Ontology (GO)? Our study provides an investigation of the functional organization of five coexpression networks using data from three mammalian organisms. Our method calculates a probabilistic score between each gene and each Gene Ontology category that reflects coexpression enrichment of a GO module. For each GO category we use Receiver Operating Curves to assess whether these probabilistic scores reflect GBA. This methodology applied to five different coexpression networks demonstrates that the signature of guilt-by-association is ubiquitous and reproducible and that the GBA heuristic is broadly applicable across the population of nine hundred Gene Ontology categories. We also demonstrate the existence of highly reproducible patterns of coexpression between some pairs of GO categories. We conclude that GBA has universal value and that transcriptional control may be more modular than previously realized. Our analyses also suggest that methodologies combining coexpression measurements across multiple genes in a biologically-defined module can aid in characterizing gene function or in characterizing whether pairs of functions operate together.
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影响因子：
7
作者：
Lee, HK;Hsu, AK;Pavlidis, P
通讯作者：
Pavlidis, P
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Ewen, ME
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作者：
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