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

Genomics. 2008 Mar;91(3):281-8. doi: 10.1016/j.ygeno.2007.11.003.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Mapping / methods
  • DNA, Complementary / genetics*
  • Gene Expression Profiling / methods*
  • Gene Library
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • RNA Caps / genetics
  • Sequence Tagged Sites
  • Transcription Initiation Site


  • DNA, Complementary
  • RNA Caps