A survey of genomic properties for the detection of regulatory polymorphisms
A survey of genomic properties for the detection of regulatory polymorphisms
复制标题
DOI：
10.1371/journal.pcbi.0030106
复制
发表时间：
2007-06-01
影响因子：
4.3
通讯作者：
Jones, Steven J. M.
中科院分区：
文献类型：
--
作者：
Montgomery, Stephen B.;Griffith, Obi L.;Jones, Steven J. M.
功能性非编码多态性的计算识别技术的进步将有助于对健康的新型决定因素进行分类，并识别解释人类进化的基因变异。然而，到目前为止，此类技术的开发和评估受到已知调控多态性的可用性的限制。我们试图通过从文献中收集并在ORegAnno数据库（http://www.oreganno.org）中构建一组在计算上易于处理的调控多态性来解决这一问题。我们进一步使用了该集合中的104个调控单核苷酸多态性以及来自基因2kb和152bp非编码上游区域的951个功能未知的多态性，以研究与基因调控和群体遗传学相关的23种特性的区分潜力。在该区域检测到的最重要的特性包括到转录起始位点的距离、局部重复内容、序列保守性、次要等位基因频率和衍生等位基因频率以及CpG岛的存在。我们进一步使用整套特性来评估它们在检测调控多态性方面的综合性能。使用10倍交叉验证方法，我们能够分别达到0.82的敏感度和0.71的特异度，并且我们表明这种性能受到到转录起始位点距离的强烈影响。
Advances in the computational identification of functional noncoding polymorphisms will aid in cataloging novel determinants of health and identifying genetic variants that explain human evolution. To date, however, the development and evaluation of such techniques has been limited by the availability of known regulatory polymorphisms. We have attempted to address this by assembling, from the literature, a computationally tractable set of regulatory polymorphisms within the ORegAnno database (http://www.oreganno.org). We have further used 104 regulatory single-nucleotide polymorphisms from this set and 951 polymorphisms of unknown function, from 2-kb and 152-bp noncoding upstream regions of genes, to investigate the discriminatory potential of 23 properties related to gene regulation and population genetics. Among the most important properties detected in this region are distance to transcription start site, local repetitive content, sequence conservation, minor and derived allele frequencies, and presence of a CpG island. We further used the entire set of properties to evaluate their collective performance in detecting regulatory polymorphisms. Using a 10-fold cross-validation approach, we were able to achieve a sensitivity and specificity of 0.82 and 0.71, respectively, and we show that this performance is strongly influenced by the distance to the transcription start site.