OrthoList: a compendium of C. elegans genes with human orthologs.

OrthoList: a compendium of C. elegans genes with human orthologs.
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DOI:
10.1371/journal.pone.0020085
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Greenwald I
Greenwald I
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shaye DD;Greenwald I

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C.线虫是人类生物学和疾病相关遗传研究的重要模型。我们试图评估C.线虫和人类基因之间的关系,以更好地了解它们的基因组之间的关系,并产生一个令人信服的候选人名单,以简化该模型中基于RNAi的筛选。我们对来自四个正字法预测程序的结果进行了荟萃分析,并生成了一个纲要,“OrthoList”,包含7,663个C。秀丽隐杆线虫蛋白质编码基因。各种评估表明,OrthoList覆盖面广,假阳性和假阴性率低。本评价的一部分检查了受体酪氨酸激酶、Notch、Wnt、TGF-β和胰岛素信号通路的组分的保守性,并使我们更新了保守的C. elegans激酶、核激素受体、F-box蛋白和转录因子。与两个已发表的全基因组RNAi筛选的比较表明,如果仅靶向OrthoList集(基因组的约38%),几乎所有的保守命中都将被获得。通过InterPro结构域和Gene Ontology注释,我们编制了Ortholist,使C.用于潜在功能分析的人类疾病基因的elegans直向同源物。我们预计,OrthoList将是相当实用的C。elegans研究人员通过关注具有明显人类直系同源物的基因来简化RNAi筛选,从而减少了60%的筛选工作。此外,我们发现,OrthoList提供了一个有用的基础上,注释正字法,并揭示了更多的C。与先前描述的相比,本发明提供了在各种功能组中的人类基因(例如转录因子)的线虫直系同源物。
C. elegans is an important model for genetic studies relevant to human biology and disease. We sought to assess the orthology between C. elegans and human genes to understand better the relationship between their genomes and to generate a compelling list of candidates to streamline RNAi-based screens in this model. We performed a meta-analysis of results from four orthology prediction programs and generated a compendium, “OrthoList”, containing 7,663 C. elegans protein-coding genes. Various assessments indicate that OrthoList has extensive coverage with low false-positive and false-negative rates. Part of this evaluation examined the conservation of components of the receptor tyrosine kinase, Notch, Wnt, TGF-ß and insulin signaling pathways, and led us to update compendia of conserved C. elegans kinases, nuclear hormone receptors, F-box proteins, and transcription factors. Comparison with two published genome-wide RNAi screens indicated that virtually all of the conserved hits would have been obtained had just the OrthoList set (∼38% of the genome) been targeted. We compiled Ortholist by InterPro domains and Gene Ontology annotation, making it easy to identify C. elegans orthologs of human disease genes for potential functional analysis. We anticipate that OrthoList will be of considerable utility to C. elegans researchers for streamlining RNAi screens, by focusing on genes with apparent human orthologs, thus reducing screening effort by ∼60%. Moreover, we find that OrthoList provides a useful basis for annotating orthology and reveals more C. elegans orthologs of human genes in various functional groups, such as transcription factors, than previously described.
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