Redefining CpG islands using hidden Markov models
Redefining CpG islands using hidden Markov models
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DOI：
10.1093/biostatistics/kxq005
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发表时间：
2010-07-01
期刊：
影响因子：
2.1
通讯作者：
Feinberg, Andrew P.
中科院分区：
文献类型：
--
作者：
Wu, Hao;Caffo, Brian;Feinberg, Andrew P.
大多数脊椎动物的DNA在CpG二核苷酸中被耗尽：在5'到3'方向上，C后跟G。CpG是DNA甲基化的靶标，DNA甲基化是细胞分裂过程中可遗传的胞嘧啶（C）的化学修饰，也是最具特征的表观遗传机制。剩余的CpG倾向于聚集在称为CpG岛（CGI）的区域中。了解CGI位置很重要，因为它们标志着发育和疾病中功能相关的表观遗传基因座。对于各种哺乳动物，包括人类，可以从UCSC基因组浏览器获得容易获得和广泛使用的CGI列表。这个列表是使用搜索满足Gardiner-Garden和Frommer在20多年前提出的CGI定义的区域的算法得出的。最近的发现，使技术的进步，允许直接测量表观遗传终点在全基因组规模，激励需要适应目前的CGI定义。在本文中，我们提出了一个程序，隐马尔可夫模型的指导下，允许一个可扩展的方法来检测CGI。我们的方法的主要优点是，它总结了CGI状态的概率分数的证据。这为CGI的定义提供了灵活性，并有助于为其他物种创建CGI列表。这种方法的效用是通过产生的第一CGI列表无脊椎动物，事实上，我们可以创建CGI列表，大大增加了重叠与最近发现的表观遗传标记。每个物种的CGI列表和概率得分，作为基因组位置的函数，可在http://www.rafalab.org上获得。
The DNA of most vertebrates is depleted in CpG dinucleotide: a C followed by a G in the 5' to 3' direction. CpGs are the target for DNA methylation, a chemical modification of cytosine (C) heritable during cell division and the most well-characterized epigenetic mechanism. The remaining CpGs tend to cluster in regions referred to as CpG islands (CGI). Knowing CGI locations is important because they mark functionally relevant epigenetic loci in development and disease. For various mammals, including human, a readily available and widely used list of CGI is available from the UCSC Genome Browser. This list was derived using algorithms that search for regions satisfying a definition of CGI proposed by Gardiner-Garden and Frommer more than 20 years ago. Recent findings, enabled by advances in technology that permit direct measurement of epigenetic endpoints at a whole-genome scale, motivate the need to adapt the current CGI definition. In this paper, we propose a procedure, guided by hidden Markov models, that permits an extensible approach to detecting CGI. The main advantage of our approach over others is that it summarizes the evidence for CGI status as probability scores. This provides flexibility in the definition of a CGI and facilitates the creation of CGI lists for other species. The utility of this approach is demonstrated by generating the first CGI lists for invertebrates, and the fact that we can create CGI lists that substantially increases overlap with recently discovered epigenetic marks. A CGI list and the probability scores, as a function of genome location, for each species are available at http://www.rafalab.org.