The GENCODE pseudogene resource.
The GENCODE pseudogene resource.
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DOI：
10.1186/gb-2012-13-9-r51
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发表时间：
2012-09-26
期刊：
影响因子：
12.3
通讯作者：
Gerstein MB
中科院分区：
文献类型：
--
作者：
Pei B;Sisu C;Frankish A;Howald C;Habegger L;Mu XJ;Harte R;Balasubramanian S;Tanzer A;Diekhans M;Reymond A;Hubbard TJ;Harrow J;Gerstein MB
假基因长期以来被视为无功能的基因组序列。然而，近期的证据表明，它们中的许多可能具有某种形式的生物学活性，其具有功能的可能性增加了人们对其准确注释以及与功能基因组学数据整合的兴趣。
作为人类基因组GENCODE注释的一部分，我们基于大规模人工注释和计算机流程，首次对蛋白质编码基因进行了全基因组范围的假基因归类。这种联合方法的一个关键方面是，它使我们能够以无偏的方式识别假基因，并通过人工评估理清复杂的事件。我们将假基因注释与大量的ENCODE功能基因组学信息相结合。特别是，我们确定了每个假基因的表达水平、转录因子和RNA聚合酶II的结合以及染色质标记。基于它们的分布，我们为每种活性类型建立了简单的统计模型，并通过大规模的RT - PCR - Seq实验对其进行验证。最后，我们将我们的假基因与来自灵长类比对和千人基因组计划的保守性和变异数据进行比较，生成了可能处于选择之下的假基因列表。
在一个极端情况下，一些假基因具有常规的功能特征；这些可能代表近期失活的基因。另一方面，我们发现了有趣的部分活性模式，这可能表明失活基因正在作为有功能的非编码RNA复活。每个假基因的活性数据都存储在一个相关的资源psiDR中，这将有助于初步识别潜在有功能的假基因。
Pseudogenes have long been considered as nonfunctional genomic sequences. However, recent evidence suggests that many of them might have some form of biological activity, and the possibility of functionality has increased interest in their accurate annotation and integration with functional genomics data. As part of the GENCODE annotation of the human genome, we present the first genome-wide pseudogene assignment for protein-coding genes, based on both large-scale manual annotation and in silico pipelines. A key aspect of this coupled approach is that it allows us to identify pseudogenes in an unbiased fashion as well as untangle complex events through manual evaluation. We integrate the pseudogene annotations with the extensive ENCODE functional genomics information. In particular, we determine the expression level, transcription-factor and RNA polymerase II binding, and chromatin marks associated with each pseudogene. Based on their distribution, we develop simple statistical models for each type of activity, which we validate with large-scale RT-PCR-Seq experiments. Finally, we compare our pseudogenes with conservation and variation data from primate alignments and the 1000 Genomes project, producing lists of pseudogenes potentially under selection. At one extreme, some pseudogenes possess conventional characteristics of functionality; these may represent genes that have recently died. On the other hand, we find interesting patterns of partial activity, which may suggest that dead genes are being resurrected as functioning non-coding RNAs. The activity data of each pseudogene are stored in an associated resource, psiDR, which will be useful for the initial identification of potentially functional pseudogenes.
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影响因子：
4.5
作者：
Frith MC;Wilming LG;Forrest A;Kawaji H;Tan SL;Wahlestedt C;Bajic VB;Kai C;Kawai J;Carninci P;Hayashizaki Y;Bailey TL;Huminiecki L
通讯作者：
Huminiecki L
影响因子：
4.8
作者：
Han, Yoo Jeong;Ma, Shwu Fan;Garcia, Joe G. N.
通讯作者：
Garcia, Joe G. N.
DOI：
10.1038/nrg2487
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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影响因子：
56.9
作者：
Duret, L;Chureau, C;Avner, P
通讯作者：
Avner, P
影响因子：
12.3
作者：
Balasubramanian S;Zheng D;Liu YJ;Fang G;Frankish A;Carriero N;Robilotto R;Cayting P;Gerstein M
通讯作者：
Gerstein M