Predicting protein function by genomic context: Quantitative evaluation and qualitative inferences
Predicting protein function by genomic context: Quantitative evaluation and qualitative inferences
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DOI：
10.1101/gr.10.8.1204
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发表时间：
2000-08-01
期刊：
影响因子：
7
通讯作者：
Bork, P
中科院分区：
文献类型：
--
作者：
Huynen, M;Snel, B;Bork, P
已经提出了各种新的方法来预测蛋白质之间的功能相互作用的基础上，其基因的基因组背景。他们使用的基因组背景类型是I型：基因的融合; II型：基因顺序的保守或潜在操纵子中基因的共现; III型：基因组中基因的共现（系统发育谱）。在这里，我们比较了这些类型的覆盖范围，它们与各种类型的功能相互作用的相关性，以及它们与基于同源性的功能分配的重叠。我们将该方法应用于生殖支原体，计算和实验基因组学中的标准基准基因组。数量上，基因顺序保守是覆盖率最高的技术，适用于37%的基因。通过将基因顺序保守与基因融合（6%）、基因在操纵子中的共现（8%）以及基因组中的共现（11%）相结合，可以获得50%的基因（类别重叠）的重要背景信息。定性地，我们观察到基因之间的功能相互作用随着对基因组上的物理邻域的要求更严格而更强，而潜在假阳性的分数降低。此外，只有在基因组的相当大一部分中基因顺序是保守的情况下，在这种情况下，25个基因组中有6个基因顺序是保守的，单一类型的功能相互作用（物理相互作用）才明显占主导地位（>80%）。在其他情况下，来自同源性搜索的互补功能信息对于预测相互作用的类型是必不可少的，所述互补功能信息可用于具有重要基因组背景的大多数基因。使用基因组背景和同源性搜索的组合，可以预测10%的M的新功能特征。生殖器基因
Various new methods have been proposed to predict Functional interactions between proteins based on the genomic context of their genes. The types of genomic context that they use are Type I: the fusion of genes; Type II: the conservation of gene-order or co-occurrence of genes in potential operons; and Type III: the co-occurrence of genes across genomes (phylogenetic profiles). Here we compare these types For their coverage, their correlations with various types of functional interaction, and their overlap with homology-based Function assignment. We apply the methods to Mycoplasma genitalium, the standard benchmarking genome in computational and experimental genomics. Quantitatively, conservation of gene order is the technique with the highest coverage, applying to 37% of the genes. By combining gene order conservation with gene fusion (6%), the co-occurrence of genes in operons in absence of gene order conservation (8%), and the co-occurrence of genes across genomes (11%), significant context information can be obtained for 50% of the genes (the categories overlap). Qualitatively, we observe that the functional interactions between genes are stronger as the requirements For physical neighborhood on the genome are more stringent, while the Fraction of potential false positives decreases. Moreover, only in cases in which gene order is conserved in a substantial Fraction of the genomes, in this case six out of twenty-five, does a single type of functional interaction (physical interaction) clearly dominate (>80%). In other cases, complementary Function information from homology searches, which is available for most of the genes with significant genomic context, is essential to predict the type of interaction. Using a combination of genomic context and homology searches, new Functional features can be predicted for 10% of M. genitalium genes.