Genetical genomics analysis of a yeast segregant population for transcription network inference
Genetical genomics analysis of a yeast segregant population for transcription network inference
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DOI：
10.1534/genetics.105.041103
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发表时间：
2005-06-01
期刊：
影响因子：
3.3
通讯作者：
Hoeschele, I
中科院分区：
文献类型：
--
作者：
Bing, N;Hoeschele, I
在整个基因组中，在DNA标记处进行了表达和基因分离的种群中基因表达的遗传分析，可以揭示多态性基因的调节网络。我们提出了一个分析策略，该策略具有多个步骤：（1）对所有表达谱的全基因组QTL分析，以识别EQTL置信区，然后对已识别的EQTL进行精细映射； （2）鉴定每个EQTL区域中的调节候选基因； （3）对任何EQTL区域中候选者的表达谱的相关性分析与受EQTL影响的基因，以减少候选者的数量； （4）从保留的监管候选基因到受EQTL影响并连接链接形成网络的基因的定向链接； （5）推断网络结构的统计验证和完善。在这里，我们将该策略的初始实施应用于分离的酵母菌种群。在65％，7％和28％中，已鉴定出的EQTL区域，单个候选调节基因，无基因或更多。比一个基因分别保留在步骤3中。总体而言，保留了768个推定的监管联系，其中331条是最强的候选链接，因为它们保留在表达相关分析中，并通过分隔多个链接QTL的多标志物分析确定的EQTL子区域内或附近。在独立的网络结构或高度互连的子网中，一个或几个生物过程在统计学上显着代表了过多的代表。推断网络中发现的大多数转录因子都有与其他基因或表现为顺式调节的推定调节链接。
Genetic analysis of gene expression in a segregating population, which is expression profiled and genotyped at DNA markers throughout the genome, can reveal regulatory networks of polymorphic genes. We propose an analysis strategy with several steps: (1) genome-wide QTL analysis of all expression profiles to identify eQTL confidence regions, followed by fine mapping of identified eQTL; (2) identification of regulatory candidate genes in each eQTL region; (3) correlation analysis of the expression profiles of the candidates in any eQTL region with the gene affected by the eQTL to reduce the number of candidates; (4) drawing directional links from retained regulatory candidate genes to genes affected by the eQTL and joining links to form networks; and (5) statistical validation and refinement of the inferred network structure. Here, we apply an initial implementation of this strategy to a segregating yeast population. In 65, 7, and 28% of the identified eQTL regions, a single candidate regulatory gene, no gene, or more. than one gene was retained in step 3, respectively. Overall, 768 putative regulatory links were retained, 331 of which are the strongest candidate links, as they were retained in the expression correlation analysis and were located within or near an eQTL subregion identified by a multimarker analysis separating multiple linked QTL. One or several biological processes were statistically significantly overrepresented in independent network structures or in highly interconnected subnetworks. Most of the transcription factors found in the inferred network had a putative regulatory link to only one other gene or exhibited cis-regulation.