oPOSSUM: identification of over-represented transcription factor binding sites in co-expressed genes.
oPOSSUM: identification of over-represented transcription factor binding sites in co-expressed genes.
复制标题
负鼠：共表达基因中代表性过多的转录因子结合位点的鉴定。
DOI：
10.1093/nar/gki624
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发表时间：
2005
影响因子：
14.9
通讯作者：
Wasserman, WW
中科院分区：
文献类型：
--
作者：
Sui, SJH;Mortimer, JR;Arenillas, DJ;Brumm, J;Walsh, CJ;Kennedy, BP;Wasserman, WW
靶向转录谱研究可以鉴定共表达基因的集合;然而，鉴定潜在的功能机制是一个重大挑战。已建立的基因注释分析方法，特别是基于基因本体论的方法，可以识别基因之间的功能联系。用于鉴定过度表达的转录因子结合位点（TFBS）的类似方法在酵母中已经成功，但扩展到人类基因组学在很大程度上被证明是无效的。建立一个系统，有效地识别共同表达的人类基因的子集中的共同调控机制，有望打破功能基因组学研究的障碍。我们已经开发了一个综合系统，搜索一个或多个转录因子（TF）的共调节的证据。oPOSSUM将人类和小鼠启动子中保守TFBS的预先计算的数据库与用于鉴定一组共表达基因中过度表达的位点的统计方法相结合。该算法成功地确定了组织特异性基因的对照组和来自三个转录谱研究的共表达基因组中的介导TF。模拟研究表明，oPOSSUM使用经验定义的阈值产生很少的假阳性，并且可以容忍一组共表达基因中高达50%的噪声。
Targeted transcript profiling studies can identify sets of co-expressed genes; however, identification of the underlying functional mechanism(s) is a significant challenge. Established methods for the analysis of gene annotations, particularly those based on the Gene Ontology, can identify functional linkages between genes. Similar methods for the identification of over-represented transcription factor binding sites (TFBSs) have been successful in yeast, but extension to human genomics has largely proved ineffective. Creation of a system for the efficient identification of common regulatory mechanisms in a subset of co-expressed human genes promises to break a roadblock in functional genomics research. We have developed an integrated system that searches for evidence of co-regulation by one or more transcription factors (TFs). oPOSSUM combines a pre-computed database of conserved TFBSs in human and mouse promoters with statistical methods for identification of sites over-represented in a set of co-expressed genes. The algorithm successfully identified mediating TFs in control sets of tissue-specific genes and in sets of co-expressed genes from three transcript profiling studies. Simulation studies indicate that oPOSSUM produces few false positives using empirically defined thresholds and can tolerate up to 50% noise in a set of co-expressed genes.
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