A rescue strategy for multimapping short sequence tags refines surveys of transcriptional activity by CAGE

Geoffrey J. Faulkner, Alistair R R Forrest, Alistair M. Chalk, Kate Schroder, Yoshihide Hayashizaki, Piero Carninci, David A. Hume, Sean M. Grimmond

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71 Citations (Scopus)

Abstract

Cap analysis gene expression (CAGE) is a high-throughput, tag-based method designed to survey the 5′ end of capped full-length cDNAs. CAGE has previously been used to define global transcription start site usage and monitor gene activity in mammals. A drawback of the CAGE approach thus far has been the removal of as many as 40% of CAGE sequence tags due to their mapping to multiple genomic locations. Here, we address the origins of multimap tags and present a novel strategy to assign CAGE tags to their most likely source promoter region. When this approach was applied to the FANTOM3 CAGE libraries, the percentage of protein-coding mouse transcriptional frameworks detected by CAGE improved from 42.9 to 57.8% (an increase of 5516 frameworks) with no reduction in CAGE to microarray correlation. These results suggest that the multimap tags produced by high-throughput, short sequence tag-based approaches can be rescued to augment greatly the transcriptome coverage provided by single-map tags alone.

Original languageEnglish
Pages (from-to)281-288
Number of pages8
JournalGenomics
Volume91
Issue number3
DOIs
Publication statusPublished - Mar 2008
Externally publishedYes

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Faulkner, G. J., Forrest, A. R. R., Chalk, A. M., Schroder, K., Hayashizaki, Y., Carninci, P., ... Grimmond, S. M. (2008). A rescue strategy for multimapping short sequence tags refines surveys of transcriptional activity by CAGE. Genomics, 91(3), 281-288. https://doi.org/10.1016/j.ygeno.2007.11.003