Identifying cell-specific microRNA transcriptional start sites
Identifying cell-specific microRNA transcriptional start sites
复制标题
识别细胞特异性 microRNA 转录起始位点
DOI：
10.1093/bioinformatics/btw171
复制
发表时间：
2016-08-15
期刊：
影响因子：
5.8
通讯作者：
Wingender, Edgar
中科院分区：
文献类型：
--
作者：
Hua, Xu;Chen, Luxiao;Wingender, Edgar
动机
microRNA（miRNA）转录起始位点（TSS）的鉴定对于理解miRNA的转录调控至关重要。由于miRNA的表达具有高度的细胞特异性，迫切需要一种自动化、系统化的方法来准确、细胞特异性地鉴定miRNA的TSSs。
结果
通过整合H3 K4 me 3和DNase I超敏位点的数据，结合保守性水平和序列特征，建立了一个识别miRNAs TSS的工作流程。通过将工作流程应用于来自ENCODE项目的54个细胞系的数据，我们成功地鉴定了663个基因内miRNAs和620个基因间miRNAs的TSS，其覆盖miRBase 18中记录的所有miRNAs的84.2%（1283/1523）。对于这些细胞系，我们发现了4042个基因内miRNA的替代TSS和3186个基因间miRNA的替代TSS。我们的方法在miRNA TSS上取得了比以前的非细胞特异性方法更好的性能。Georgakilas等人开发的细胞特异性方法在两种细胞系中提供了158个更高准确度的TSS，这得益于深度测序技术的应用。相比之下，我们的方法为更广泛的细胞系提供了更高数量的miRNA TSS（7228），而没有昂贵的深度测序数据的限制，因此更适用于各种实验情况。分析表明，上游启动子在TSS的-2 kb到-200 bp处对于独立转录的miRNA更为保守，而对于与宿主基因一起转录的miRNA，其核心启动子（TSS的-200 bp到200 bp）是显著保守的。
可用性和执行
预测的miRNA TSS和启动子可以从补充文件中下载。
接触
jwang@nju.edu.cn或jlee@nju.edu.cn或埃德加. bioinf.med.uni-goettingen.de
补充资料
补充数据可在Bioinformatics在线获得。
MOTIVATION
Identification of microRNA (miRNA) transcriptional start sites (TSSs) is crucial to understand the transcriptional regulation of miRNA. As miRNA expression is highly cell specific, an automatic and systematic method that could identify miRNA TSSs accurately and cell specifically is in urgent requirement.
RESULTS
A workflow to identify the TSSs of miRNAs was built by integrating the data of H3K4me3 and DNase I hypersensitive sites as well as combining the conservation level and sequence feature. By applying the workflow to the data for 54 cell lines from the ENCODE project, we successfully identified TSSs for 663 intragenic miRNAs and 620 intergenic miRNAs, which cover 84.2% (1283/1523) of all miRNAs recorded in miRBase 18. For these cell lines, we found 4042 alternative TSSs for intragenic miRNAs and 3186 alternative TSSs for intergenic miRNAs. Our method achieved a better performance than the previous non-cell-specific methods on miRNA TSSs. The cell-specific method developed by Georgakilas et al. gives 158 TSSs of higher accuracy in two cell lines, benefitting from the employment of deep-sequencing technique. In contrast, our method provided a much higher number of miRNA TSSs (7228) for a broader range of cell lines without the limitation of costly deep-sequencing data, thus being more applicable for various experimental cases. Analysis showed that upstream promoters at - 2 kb to - 200 bp of TSS are more conserved for independently transcribed miRNAs, while for miRNAs transcribed with host genes, their core promoters (-200 bp to 200 bp of TSS) are significantly conserved.
AVAILABILITY AND IMPLEMENTATION
Predicted miRNA TSSs and promoters can be downloaded from supplementary files.
CONTACT
jwang@nju.edu.cn or jlee@nju.edu.cn or edgar.wingender@bioinf.med.uni-goettingen.de
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.