Aging mice show a decreasing correlation of gene expression within genetic modules.
Aging mice show a decreasing correlation of gene expression within genetic modules.
复制标题
DOI：
10.1371/journal.pgen.1000776
复制
发表时间：
2009-12
期刊：
影响因子：
4.5
通讯作者：
Kim SK
中科院分区：
文献类型：
--
作者：
Southworth LK;Owen AB;Kim SK
在这项工作中，我们提出了一种对基因共表达网络进行差异分析的方法，并应用该方法来寻找衰老过程中的大规模转录变化。我们从16月龄和24月龄小鼠的AGEMAP表达数据中推导出同义基因共表达网络。我们确定了一些功能基因组，它们会随着年龄的变化而改变共表达。在这些变化的群体中，我们发现随着年龄的增长，相关性有下降的趋势。特别是，我们发现与年龄的总体相关性呈模块化(而不是一致)下降。我们确定了可能有助于模块相关性下降的潜在转录机制。我们发现，通过计算识别的核因子-ΚB转录因子的靶标降低了与年龄的相关性。最后，我们发现，容易降低共表达的基因往往位于染色体上。我们的结果得出结论，在小鼠中，随着年龄的增长，共表达出现了模块化的下降。他们还表明，与染色体结构域和特定转录因子相关的因素可能是导致这种下降的原因。越来越多的证据表明，哺乳动物的衰老是以基因转录变异增加为标志的。这一趋势不仅通过研究单个细胞中的基因表达而显示出来(Bahar等人。2006)，但在粗组织分辨率下也是如此(Somel等人。2006年；Li等人。2009年)。这让我们相信，仅看表达水平的绝对变化可能不能反映年龄转录变化的全部情况。相反，故事可能发生在多个基因之间表达协调的更微妙的变化中。出于这个原因，我们决定观察共表达关系随年龄的变化。为此，我们开发了一种用于全球范围内比较基因共表达的差异共表达网络分析方法。我们应用这种方法来比较年轻(16个月)和老年(24个月)小鼠之间的共同表达。这使我们能够找到其协调性似乎受到年龄影响的两个基因组，并提出这种变化的潜在机制。我们相信我们的工作具有广泛的重要性，因为它代表了一种不同的范式，不仅可以研究衰老，还可以研究任何复杂的疾病或疾病-从单个基因的变化到基因关系的变化。
In this work we present a method for the differential analysis of gene co-expression networks and apply this method to look for large-scale transcriptional changes in aging. We derived synonymous gene co-expression networks from AGEMAP expression data for 16-month-old and 24-month-old mice. We identified a number of functional gene groups that change co-expression with age. Among these changing groups we found a trend towards declining correlation with age. In particular, we identified a modular (as opposed to uniform) decline in general correlation with age. We identified potential transcriptional mechanisms that may aid in modular correlation decline. We found that computationally identified targets of the NF-ΚB transcription factor decrease expression correlation with age. Finally, we found that genes that are prone to declining co-expression tend to be co-located on the chromosome. Our results conclude that there is a modular decline in co-expression with age in mice. They also indicate that factors relating to both chromosome domains and specific transcription factors may contribute to the decline. There is mounting evidence that mammalian aging is marked by increased gene transcriptional variation. This trend was shown not only by studying gene expression in single cells (Bahar et al. 2006), but at the coarse tissue resolution as well (Somel et al. 2006; Li et al. 2009). These led us to believe that looking at absolute changes in expression level alone may not tell the whole story of transcriptional changes in age. Instead the story may be in the more subtle changes in the coordination of expression among multiple genes. For this reason, we decided to look at changes in co-expression relationships with age. To this end, we developed a methodology for differential co-expression network analysis for the comparison gene co-expression on a global scale. We applied this methodology to compare co-expression between young (16-month) and old (24-month) mice. This allowed us to find both gene groups whose coordination appear to be affected by age and to propose potential mechanisms for the change. We believe our work is of broad importance because it represents a different paradigm for looking not only at aging but also at any complex condition or disease—away from changes in individual genes towards changes in gene relationships.
登录
查看更多内容
影响因子：
7
作者：
Lee, HK;Hsu, AK;Pavlidis, P
通讯作者：
Pavlidis, P
影响因子：
46.9
作者：
Butte, AJ;Kohane, IS
通讯作者：
Kohane, IS
影响因子：
10.7
作者：
Jordan, IK;Mariño-Ramírez, L;Koonin, EV
通讯作者：
Koonin, EV
DOI：
10.1073/pnas.0610772104
发表时间：
2007-02-06
影响因子：
11.1
作者：
Duarte, Natalie C.;Becker, Scott A.;Palsson, Bernhard O.
通讯作者：
Palsson, Bernhard O.
影响因子：
14.9
作者：
Hinrichs AS;Karolchik D;Baertsch R;Barber GP;Bejerano G;Clawson H;Diekhans M;Furey TS;Harte RA;Hsu F;Hillman-Jackson J;Kuhn RM;Pedersen JS;Pohl A;Raney BJ;Rosenbloom KR;Siepel A;Smith KE;Sugnet CW;Sultan-Qurraie A;Thomas DJ;Trumbower H;Weber RJ;Weirauch M;Zweig AS;Haussler D;Kent WJ
通讯作者：
Kent WJ