Using hexamers to predict cis-regulatory motifs in Drosophila

Using hexamers to predict cis-regulatory motifs in Drosophila
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DOI:
10.1186/1471-2105-6-262
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发表时间:
2005-10-27
期刊:
影响因子:
3
通讯作者:
Kibler, D
Kibler, D
中科院分区:
生物学4区
文献类型:
--
作者:
Chan, BY;Kibler, D

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背景:顺式调控模块(CRMs)是高等真核生物中帮助调控基因表达的DNA短片段。它们被发现与它们调控的基因相距1兆碱基,可以位于上游、下游,甚至在它们的靶基因内。由于使用生物和计算技术发现标准物质的困难,即使是经过充分研究的监管系统可能包含标准物质,尚未被发现。结果:我们提出了一个简单,有效的方法(HexDiff)仅基于六聚体频率的已知标准物质和非标准物质序列预测新的标准物质在监管系统。在包含52个已知CRM的16个缺口和配对规则基因的数据集上,HexDiff做出的预测与已知CRM的相关性高于几种现有的CRM预测算法:Ahab、Cluster Buster、MSCAN、MCAST和LWF。在结合不同算法的结果后,确定了10个假定的标准物质,并且是未来研究的有力候选者。HexDiff用于区分CRM和非CRM序列的六聚体也进行了分析,并被证明是丰富的regulatory elements.Conclusion:HexDiff提供了一种高效和有效的手段,用于发现新的CRM的基础上已知的CRM,而不是已知的结合位点。
Background: Cis-regulatory modules (CRMs) are short stretches of DNA that help regulate gene expression in higher eukaryotes. They have been found up to 1 megabase away from the genes they regulate and can be located upstream, downstream, and even within their target genes. Due to the difficulty of finding CRMs using biological and computational techniques, even well-studied regulatory systems may contain CRMs that have not yet been discovered.Results: We present a simple, efficient method (HexDiff) based only on hexamer frequencies of known CRMs and non-CRM sequence to predict novel CRMs in regulatory systems. On a data set of 16 gap and pair-rule genes containing 52 known CRMs, predictions made by HexDiff had a higher correlation with the known CRMs than several existing CRM prediction algorithms: Ahab, Cluster Buster, MSCAN, MCAST, and LWF. After combining the results of the different algorithms, 10 putative CRMs were identified and are strong candidates for future study. The hexamers used by HexDiff to distinguish between CRMs and non-CRM sequence were also analyzed and were shown to be enriched in regulatory elements.Conclusion: HexDiff provides an efficient and effective means for finding new CRMs based on known CRMs, rather than known binding sites.