Setting CAGE Tags in a Genomic Context

The detection and quantification of transcriptional activity on the genome by CAGE requires reliable and high-throughput tag mapping. Here, we discuss the basic considerations of sequence tag mapping and how these apply to CAGE. The current CAGE mapping pipeline is then described in detail, in particular how it has been updated to utilize iterative global exact matching for each tag rather than heuristic algorithm local alignment. Combined with the addition of a novel method to resolve tags that map to multiple genomic locations, the most recent evolution of the CAGE mapping pipeline is faster, more accurate and provides better coverage than the previous approach, as we demonstrate using a sample CAGE library. Finally, the pipeline is easily customized for other sequence tag technologies, suggesting broad utility in the era of next-generation sequencing.