An integrative and applicable phylogenetic footprinting framework for cis-regulatory motifs identification in prokaryotic genomes.
An integrative and applicable phylogenetic footprinting framework for cis-regulatory motifs identification in prokaryotic genomes.
复制标题
用于原核基因组中顺式调控基序识别的综合且适用的系统发育足迹框架
DOI：
10.1186/s12864-016-2982-x
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发表时间：
2016-08-09
期刊：
影响因子：
4.4
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Liu B;Zhang H;Zhou C;Li G;Fennell A;Wang G;Kang Y;Liu Q;Ma Q
背景系统发育足迹是一种重要的计算技术，用于识别多个基因组直系同源调节区中的顺式调节基序，因为基序往往比其周围的非功能序列进化得更慢。然而，它的应用程序，有几个困难，优化选择的orthopathic数据和减少假阳性motif prediction.ResultsHere，我们提出了一个完整的系统发育足迹框架准确的基序预测在原核生物基因组（MP3）。该框架包括一个新的orthopathic数据准备程序，一个额外的启动子评分和修剪方法和一个集成的六个现有的基序查找算法作为基本的基序搜索引擎。具体来说，我们收集了原核基因组中的正向同源基因，并根据启动子区的序列相似性构建了正向同源调控区。该方法充分利用了大规模基因组数据和分类学信息，筛选出了贡献有限的启动子，从而获得了高质量的直向启动子集。启动子评分和修剪是通过一组互补的预测工具，挖掘尽可能多的模体候选人，同时消除随机噪声的影响，通过模体投票实现的。我们已经将该框架应用于大肠杆菌k12基因组，并通过与七个现有程序的比较来评估预测性能。该评估在核苷酸和结合位点水平上系统地进行，结果表明MP3始终优于其他流行的基序发现工具。我们已经将MP3集成到我们的基序识别和分析服务器DMINDA中，允许用户有效地识别和分析2,072个完全测序的原核基因组中的基序。它的应用可能会促进阐明转录调控机制的进展，从而为基因组研究界，特别是原核基因组研究者提供有益的帮助。
BackgroundPhylogenetic footprinting is an important computational technique for identifying cis-regulatory motifs in orthologous regulatory regions from multiple genomes, as motifs tend to evolve slower than their surrounding non-functional sequences. Its application, however, has several difficulties for optimizing the selection of orthologous data and reducing the false positives in motif prediction.ResultsHere we present an integrative phylogenetic footprinting framework for accurate motif predictions in prokaryotic genomes (MP3). The framework includes a new orthologous data preparation procedure, an additional promoter scoring and pruning method and an integration of six existing motif finding algorithms as basic motif search engines. Specifically, we collected orthologous genes from available prokaryotic genomes and built the orthologous regulatory regions based on sequence similarity of promoter regions. This procedure made full use of the large-scale genomic data and taxonomy information and filtered out the promoters with limited contribution to produce a high quality orthologous promoter set. The promoter scoring and pruning is implemented through motif voting by a set of complementary predicting tools that mine as many motif candidates as possible and simultaneously eliminate the effect of random noise. We have applied the framework to Escherichia coli k12 genome and evaluated the prediction performance through comparison with seven existing programs. This evaluation was systematically carried out at the nucleotide and binding site level, and the results showed that MP3 consistently outperformed other popular motif finding tools. We have integrated MP3 into our motif identification and analysis server DMINDA, allowing users to efficiently identify and analyze motifs in 2,072 completely sequenced prokaryotic genomes.ConclusionThe performance evaluation indicated that MP3 is effective for predicting regulatory motifs in prokaryotic genomes. Its application may enhance progress in elucidating transcription regulation mechanism, thus provide benefit to the genomic research community and prokaryotic genome researchers in particular.