G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes
G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes
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DOI：
10.1186/1471-2105-13-253
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发表时间：
2012-09-28
影响因子：
3
通讯作者：
Pollard, Katherine S.
中科院分区：
文献类型：
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作者：
Lemay, Danielle G.;Martin, William F.;Pollard, Katherine S.
背景资料：在以前的研究中，基因邻域-基因组中共表达基因的空间簇-已经使用任意的规则来定义，例如要求邻接、最小基因数、固定窗口大小或最小表达水平。在目前的研究中，我们开发了一个基因邻域评分工具（G-NEST），它结合了基因组位置，基因表达，和进化序列保守性的数据，在所有可能的窗口sizes.Results的分数推定的基因邻域：使用G-NEST对小鼠和人类组织表达数据的图谱，我们发现，10个或更多的基因的大邻居是非常罕见的哺乳动物基因组。当它们发生时，邻域通常由相关基因的家族组成。哺乳动物基因组中得分最高和最大的邻域都是由串联基因复制形成的。哺乳动物基因邻域包含高表达和低表达的基因。共定位的噪声基因对表现出较低的进化保守性，其相邻的基因组位置，这表明他们共享的转录背景可能是不利的。哺乳动物生存和繁殖所必需的基因不太可能出现在社区中，尽管社区富含有丝分裂功能的基因。我们还发现，基因的方向和蛋白质-蛋白质相互作用是部分负责维护的基因neighbors.Conclusions：我们的实验使用G-NEST证实，串联基因重复是在哺乳动物基因组中的非随机基因顺序的主要驱动程序。非必要性、共功能性、基因方向和蛋白质-蛋白质相互作用是维持基因邻域的额外力量，特别是那些由串联重复形成的基因。我们希望G-NEST是有用的其他应用，如核心调控模块，共同的转录背景，和染色质结构域的识别。该软件可在http://docpollard.org/software.html上获得
Background: In previous studies, gene neighborhoods-spatial clusters of co-expressed genes in the genome-have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Scoring Tool (G-NEST) which combines genomic location, gene expression, and evolutionary sequence conservation data to score putative gene neighborhoods across all possible window sizes simultaneously.Results: Using G-NEST on atlases of mouse and human tissue expression data, we found that large neighborhoods of ten or more genes are extremely rare in mammalian genomes. When they do occur, neighborhoods are typically composed of families of related genes. Both the highest scoring and the largest neighborhoods in mammalian genomes are formed by tandem gene duplication. Mammalian gene neighborhoods contain highly and variably expressed genes. Co-localized noisy gene pairs exhibit lower evolutionary conservation of their adjacent genome locations, suggesting that their shared transcriptional background may be disadvantageous. Genes that are essential to mammalian survival and reproduction are less likely to occur in neighborhoods, although neighborhoods are enriched with genes that function in mitosis. We also found that gene orientation and protein-protein interactions are partially responsible for maintenance of gene neighborhoods.Conclusions: Our experiments using G-NEST confirm that tandem gene duplication is the primary driver of non-random gene order in mammalian genomes. Non-essentiality, co-functionality, gene orientation, and protein-protein interactions are additional forces that maintain gene neighborhoods, especially those formed by tandem duplicates. We expect G-NEST to be useful for other applications such as the identification of core regulatory modules, common transcriptional backgrounds, and chromatin domains. The software is available at http://docpollard.org/software.html