A comprehensive functional analysis of tissue specificity of human gene expression.
A comprehensive functional analysis of tissue specificity of human gene expression.
复制标题
人类基因表达的组织特异性的综合功能分析。
DOI：
10.1186/1741-7007-6-49
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发表时间：
2008-11-12
期刊：
影响因子：
5.4
通讯作者：
Nikolskaya T
中科院分区：
文献类型：
--
作者：
Dezso Z;Nikolsky Y;Sviridov E;Shi W;Serebriyskaya T;Dosymbekov D;Bugrim A;Rakhmatulin E;Brennan RJ;Guryanov A;Li K;Blake J;Samaha RR;Nikolskaya T
近年来，微阵列技术的成熟已经允许基因表达模式的全基因组分析，以确定组织特异性和普遍表达（“管家”）的基因。我们对管家和组织特异性网络进行了功能和拓扑分析，以确定普遍必要的生物过程，以及特定组织特有的或具有特定组织特征的生物过程。我们测量了31个人体组织中的全基因组表达，确定了2374个在所有组织中表达的管家基因，以及在每个组织中唯一表达的基因。全面的功能分析表明，管家集比以前认为的要大得多，并且富含重要的过程，如氧化磷酸化，泛素依赖的蛋白水解，翻译和能量代谢。管家网络的网络拓扑结构的特点是更高的连接性和更短的蛋白质之间的路径比全球网络。组织特异性基因的本体富集评分和网络拓扑结构与每个组织的功能和表达模式一致，并根据组织来源聚集在一起。组织特异性基因成为药物靶点的可能性是管家基因的两倍，从而可以识别组织“签名网络”，这将有助于发现新的治疗靶点和组织靶向疾病的生物标志物。对管家基因和组织特异性基因的功能分析表明，管家基因和组织特异性基因的生物学功能与组织起源一致。网络分析显示，组织特异性网络具有与每个组织的功能相关的不同网络特性。组织“特征网络”有望成为疾病治疗和诊断的靶点和生物标志物的丰富来源。
In recent years, the maturation of microarray technology has allowed the genome-wide analysis of gene expression patterns to identify tissue-specific and ubiquitously expressed ('housekeeping') genes. We have performed a functional and topological analysis of housekeeping and tissue-specific networks to identify universally necessary biological processes, and those unique to or characteristic of particular tissues. We measured whole genome expression in 31 human tissues, identifying 2374 housekeeping genes expressed in all tissues, and genes uniquely expressed in each tissue. Comprehensive functional analysis showed that the housekeeping set is substantially larger than previously thought, and is enriched with vital processes such as oxidative phosphorylation, ubiquitin-dependent proteolysis, translation and energy metabolism. Network topology of the housekeeping network was characterized by higher connectivity and shorter paths between the proteins than the global network. Ontology enrichment scoring and network topology of tissue-specific genes were consistent with each tissue's function and expression patterns clustered together in accordance with tissue origin. Tissue-specific genes were twice as likely as housekeeping genes to be drug targets, allowing the identification of tissue 'signature networks' that will facilitate the discovery of new therapeutic targets and biomarkers of tissue-targeted diseases. A comprehensive functional analysis of housekeeping and tissue-specific genes showed that the biological function of housekeeping and tissue-specific genes was consistent with tissue origin. Network analysis revealed that tissue-specific networks have distinct network properties related to each tissue's function. Tissue 'signature networks' promise to be a rich source of targets and biomarkers for disease treatment and diagnosis.
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影响因子：
4.4
作者：
Tu Z;Wang L;Xu M;Zhou X;Chen T;Sun F
通讯作者：
Sun F
DOI：
10.1073/pnas.1635054100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Schultz, N;Hamra, FK;Garbers, DL
通讯作者：
Garbers, DL
影响因子：
4.4
作者：
Kouadjo KE;Nishida Y;Cadrin-Girard JF;Yoshioka M;St-Amand J
通讯作者：
St-Amand J
影响因子：
9.9
作者：
通讯作者：
--
影响因子：
7
作者：
Callow, MJ;Dudoit, S;Rubin, EM
通讯作者：
Rubin, EM