Mapping high throughput sequencing data to a reference genome is an essential step for most existing analysis pipelines aiming at the computational analysis of genome and transcriptome sequencing data. Breaking ties between equally likely mapping locations still poses a severe problem not only during the alignment phase but also has significant impact how the data can be used for further analyses. We present the multimapper resolution (MMR) tool that infers an optimal mapping location only on the distribution of mapped reads.

Principle

We follow a quite simple strategy that locally minimizes the variance of position wise coverage within windows around two possible mapping locations. Comparing the local "roughness" around two possible mappings, we can iteratively optimize all mappings to converge to a globally "smooth" coverage. Additional information, e.g., transcript structure, to accounting for expected differences in local coverage can be incorporated. The following figure illustrates the MMR principle.