RECLU: a pipeline to discover reproducible transcriptional start sites and their alternative regulation using capped analysis of gene expression (CAGE)

BMC Genomics

Timo Lassmann¹  Yoshihide Hayashizaki²  Alistair RR Forrest¹  Piero Carninci¹  Masayoshi Itoh²  Martin C Frith³  Morana Vitezic⁴  Hiroko Ohmiya⁵ 

[1] RIKEN Center for Life Science Technologies (CLST), Division of Genomic Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, 230-0045 Yokohama, Japan;RIKEN Preventive Medicine and Diagnosis Innovation Program (PMI), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, 230-0045 Yokohama, Japan;Sequence Analysis Team, Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, 135-0064 Tokyo, Japan;Bioinformatics Centre, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark;RIKEN Advanced Center for Computing and Communication, Preventive Medicine and Applied Genomics Unit, 1-7-22 Suehiro-cho, Tsurumi-ku, 230-0045 Yokohama, Japan

关键词: Hierarchical stability;    Reproducibility;    Peak finding;    CAGE;   

Others  :  1217395
DOI  :  10.1186/1471-2164-15-269

 received in 2014-01-16, accepted in 2014-04-04,  发布年份 2014

【 摘 要 】

Background

Next generation sequencing based technologies are being extensively used to study transcriptomes. Among these, cap analysis of gene expression (CAGE) is specialized in detecting the most 5’ ends of RNA molecules. After mapping the sequenced reads back to a reference genome CAGE data highlights the transcriptional start sites (TSSs) and their usage at a single nucleotide resolution.

Results

We propose a pipeline to group the single nucleotide TSS into larger reproducible peaks and compare their usage across biological states. Importantly, our pipeline discovers broad peaks as well as the fine structure of individual transcriptional start sites embedded within them. We assess the performance of our approach on a large CAGE datasets including 156 primary cell types and two cell lines with biological replicas. We demonstrate that genes have complicated structures of transcription initiation events. In particular, we discover that narrow peaks embedded in broader regions of transcriptional activity can be differentially used even if the larger region is not.

Conclusions

By examining the reproducible fine scaled organization of TSS we can detect many differentially regulated peaks undetected by previous approaches.

【 授权许可】

   
2014 Ohmiya et al.; licensee BioMed Central Ltd.

【 图 表 】

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