Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification
Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification
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DOI：
10.1093/bioinformatics/bti042
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发表时间：
2005-03-01
期刊：
影响因子：
5.8
通讯作者：
Shmueli, O
中科院分区：
文献类型：
--
作者：
Yanai, I;Benjamin, H;Shmueli, O
动机：基因通常被分为管家基因或单组织特异性基因。我们强调，关键的功能信息驻留在基因的中档profiles of expression.Results：为了获得这种新的信息全基因组，我们已经确定了迄今为止最大的一组62 839 probesets在12个有代表性的正常人体组织的mRNA表达水平。事实上，当使用新定义的分级组织特异性指数tau时，值在管家基因的0和组织特异性基因的1之间，具有中等分布的基因具有< 0.85 were found to constitute >所有表达模式的0.15 < tau 50%。我们开发了一个二元分类，指出每个基因的I（B）组织中，它是过度表达，和12 - I（B）组织中，它显示低表达。85个优势中程模式与I（B）= 2-11被认为是双峰分布，并有助于最显着的组织规格树状图的定义。我们的分析提供了一种新的途径来推断组织树状图中假定的祖先节点的表达谱。这样的定义揭示了一个未被怀疑的相关性，即基因表达的从头增强和减少齐头并进。这些发现突出了基因抑制事件的重要性，与个体发育和胚胎发育的组织规格的过程中的影响。
Motivation: Genes are often characterized dichotomously as either housekeeping or single-tissue specific. We conjectured that crucial functional information resides in genes with midrange profiles of expression.Results: To obtain such novel information genome-wide, we have determined the mRNA expression levels for one of the largest hitherto analyzed set of 62 839 probesets in 12 representative normal human tissues. Indeed, when using a newly defined graded tissue specificity index tau, valued between 0 for housekeeping genes and 1 for tissue-specific genes, genes with midrange profiles having 0.15 < tau < 0.85 were found to constitute >50% of all expression patterns. We developed a binary classification, indicating for every gene the I (B) tissues in which it is overly expressed, and the 12 - I (B) tissues in which it shows low expression. The 85 dominant midrange patterns with I (B) = 2-11 were found to be bimodally distributed, and to contribute most significantly to the definition of tissue specification dendrograms. Our analyses provide a novel route to infer expression profiles for presumed ancestral nodes in the tissue dendrogram. Such definition has uncovered an unsuspected correlation, whereby de novo enhancement and diminution of gene expression go hand in hand. These findings highlight the importance of gene suppression events, with implications to the course of tissue specification in ontogeny and phylogeny.