CpGcluster: a distance-based algorithm for CpG-island detection.
CpGcluster: a distance-based algorithm for CpG-island detection.
复制标题
DOI：
10.1186/1471-2105-7-446
复制
发表时间：
2006-10-12
影响因子：
3
通讯作者：
Oliver JL
中科院分区：
文献类型：
--
作者：
Hackenberg M;Previti C;Luque-Escamilla PL;Carpena P;Martínez-Aroza J;Oliver JL
尽管它们参与基因表达的调控和它们作为基因组标记物用于启动子预测的重要性，但是不存在用于定义CpG岛（CGI）的客观标准，因为所有当前方法都依赖于由长度、CpG分数和G+C含量的阈值形成的大的参数空间。鉴于CGI处CpG二核苷酸的频率较高，与本体DNA相比，相邻CpG之间的距离分布对于本体和岛状CpG应该不同。提出了一种新的算法（CpGcluster），该算法基于染色体上相邻CpGs之间的物理距离，能够直接预测CpGs的聚类，而不依赖于上述主观标准。通过为这些聚类中的每个聚类分配p值，可以将统计学上最显著的聚类预测为CGI。通过使用从实验CGI文库组装的测试序列集，将CpGcluster与其他五个CGI发现者进行基准测试。CpGcluster达到了最高的总体准确度值，同时显示出最低的假阳性预测率。由于不需要最小长度阈值，CpGcluster可以找到其他算法通常错过的短但功能完整的CGI。由CpG聚类预测的CGIs与Alu反转录转座子的重叠程度最低，同时与脊椎动物系统发育保守元件（PhastCons）的重叠程度最高。与其他基因组位置中的岛相比，与转录起始位点（TSS）重叠的CpGcluster的CGI显示出最高的统计显著性，从而使CpGcluster有资格作为区分功能性CGI与本体基因组中的剩余岛的有价值的工具。CpGcluster仅使用整数运算，因此是一种快速且计算效率高的算法，能够预测CpG二核苷酸的统计学显著簇。另一个突出的特征是所有预测的CGI都以CpG二核苷酸开始和结束，这应该适合于其功能性精确基于CpG二核苷酸的基因组特征。与以往的算法相比，该算法的唯一搜索参数是两个连续CpG之间的距离。因此，不需要CpG岛的主要统计特性（既不G+C含量、CpG分数也不长度阈值）作为搜索参数，这可能导致对于CpG簇预测观察到的高特异性和与假Alu元件的低重叠。
Despite their involvement in the regulation of gene expression and their importance as genomic markers for promoter prediction, no objective standard exists for defining CpG islands (CGIs), since all current approaches rely on a large parameter space formed by the thresholds of length, CpG fraction and G+C content. Given the higher frequency of CpG dinucleotides at CGIs, as compared to bulk DNA, the distance distributions between neighboring CpGs should differ for bulk and island CpGs. A new algorithm (CpGcluster) is presented, based on the physical distance between neighboring CpGs on the chromosome and able to predict directly clusters of CpGs, while not depending on the subjective criteria mentioned above. By assigning a p-value to each of these clusters, the most statistically significant ones can be predicted as CGIs. CpGcluster was benchmarked against five other CGI finders by using a test sequence set assembled from an experimental CGI library. CpGcluster reached the highest overall accuracy values, while showing the lowest rate of false-positive predictions. Since a minimum-length threshold is not required, CpGcluster can find short but fully functional CGIs usually missed by other algorithms. The CGIs predicted by CpGcluster present the lowest degree of overlap with Alu retrotransposons and, simultaneously, the highest overlap with vertebrate Phylogenetic Conserved Elements (PhastCons). CpGcluster's CGIs overlapping with the Transcription Start Site (TSS) show the highest statistical significance, as compared to the islands in other genome locations, thus qualifying CpGcluster as a valuable tool in discriminating functional CGIs from the remaining islands in the bulk genome. CpGcluster uses only integer arithmetic, thus being a fast and computationally efficient algorithm able to predict statistically significant clusters of CpG dinucleotides. Another outstanding feature is that all predicted CGIs start and end with a CpG dinucleotide, which should be appropriate for a genomic feature whose functionality is based precisely on CpG dinucleotides. The only search parameter in CpGcluster is the distance between two consecutive CpGs, in contrast to previous algorithms. Therefore, none of the main statistical properties of CpG islands (neither G+C content, CpG fraction nor length threshold) are needed as search parameters, which may lead to the high specificity and low overlap with spurious Alu elements observed for CpGcluster predictions.
登录
查看更多内容
影响因子：
3.5
作者：
Baylin, SB;Esteller, M;Herman, JG
通讯作者：
Herman, JG
影响因子：
30.8
作者：
Futscher, BW;Oshiro, MM;Domann, FE
通讯作者：
Domann, FE
影响因子：
3.5
作者：
Li, WT
通讯作者：
Li, WT
影响因子：
5.8
作者：
Ponger, L;Mouchiroud, D
通讯作者：
Mouchiroud, D
影响因子：
78.5
作者：
Issa, JP
通讯作者：
Issa, JP