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

TY - JOUR

T1 - RECLU

T2 - a pipeline to discover reproducible transcriptional start sites and their alternative regulation using capped analysis of gene expression (CAGE)

AU - Ohmiya, Hiroko

AU - Vitezic, Morana

AU - Frith, Martin C.

AU - Itoh, Masayoshi

AU - Carninci, Piero

AU - Forrest, Alistair R.R.

AU - Hayashizaki, Yoshihide

AU - Lassmann, Timo

AU - The FANTOM Consortium

PY - 2014/4/25

Y1 - 2014/4/25

N2 - 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.

AB - 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.

U2 - 10.1186/1471-2164-15-269

DO - 10.1186/1471-2164-15-269

M3 - Journal article

C2 - 24779366

SN - 1471-2164

VL - 15

JO - BMC Genomics

JF - BMC Genomics

M1 - 269

ER -