全基因组中程转录谱揭示了人类组织特化中的表达水平关系。

Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification.

作者信息

Yanai Itai, Benjamin Hila, Shmoish Michael, Chalifa-Caspi Vered, Shklar Maxim, Ophir Ron, Bar-Even Arren, Horn-Saban Shirley, Safran Marilyn, Domany Eytan, Lancet Doron, Shmueli Orit

机构信息

Department of Molecular Genetics, Weizmann Institute of Science 76100 Rehovot, Israel.

出版信息

Bioinformatics. 2005 Mar 1;21(5):650-9. doi: 10.1093/bioinformatics/bti042. Epub 2004 Sep 23.

DOI:10.1093/bioinformatics/bti042

PMID:15388519

Abstract

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.

AVAILABILITY

All data and analyses are publically available at the GeneNote website, http://genecards.weizmann.ac.il/genenote/ and, GEO accession GSE803.

CONTACT

doron.lancet@weizmann.ac.il

SUPPLEMENTARY INFORMATION

Four tables available at the above site.

摘要

动机

基因通常被二分法地描述为管家基因或单组织特异性基因。我们推测关键的功能信息存在于具有中等表达谱的基因中。

结果

为了在全基因组范围内获得此类新信息，我们测定了12种代表性正常人体组织中迄今为止分析的最大的62839个探针集之一的mRNA表达水平。实际上，当使用新定义的分级组织特异性指数tau（管家基因的值为0，组织特异性基因的值为1）时，发现tau值在0.15 < tau < 0.85之间的中等表达谱基因构成了所有表达模式的50%以上。我们开发了一种二元分类法，为每个基因指明其过度表达的I(B)组织以及表达水平较低的12 - I(B)组织。发现I(B)=2 - 11的85种主要中等表达模式呈双峰分布，并且对组织特异性树状图的定义贡献最为显著。我们的分析提供了一种新途径来推断组织树状图中假定祖先节点的表达谱。这样的定义揭示了一种未被怀疑的相关性，即基因表达的从头增强和减弱是相伴发生的。这些发现突出了基因抑制事件的重要性，对个体发育和系统发育中组织特异性的过程具有启示意义。