A rescue strategy for multimapping short sequence tags refines surveys of transcriptional activity by CAGE. Faulkner, G., J., Forrest, A., R., Chalk, A., M., Schroder, K., Hayashizaki, Y., Carninci, P., Hume, D., A., & Grimmond, S., M. Genomics, 91(3):281-288, 2008.
A rescue strategy for multimapping short sequence tags refines surveys of transcriptional activity by CAGE [pdf]Paper  abstract   bibtex   
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.

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