%0 Journal Article %A Davide Verzotto %A Audrey S.M. Teo %A Axel M. Hillmer %A Niranjan Nagarajan %T Index-based map-to-sequence alignment in large eukaryotic genomes %D 2015 %R 10.1101/017194 %J bioRxiv %P 017194 %X Resolution of complex repeat structures and rearrangements in the assembly and analysis of large eukaryotic genomes is often aided by a combination of high-throughput sequencing and mapping technologies (e.g. optical restriction mapping). In particular, mapping technologies can generate sparse maps of large DNA fragments (150 kbp–2 Mbp) and thus provide a unique source of information for disambiguating complex rearrangements in cancer genomes. Despite their utility, combining high-throughput sequencing and mapping technologies has been challenging due to the lack of efficient and freely available software for robustly aligning maps to sequences. Here we introduce two new map-to-sequence alignment algorithms that efficiently and accurately align high-throughput mapping datasets to large, eukaryotic genomes while accounting for high error rates. In order to do so, these methods (OPTIMA for glocal and OPTIMA-Overlap for overlap alignment) exploit the ability to create efficient data structures that index continuous-valued mapping data while accounting for errors. We also introduce an approach for evaluating the significance of alignments that avoids expensive permutation-based tests while being agnostic to technology-dependent error rates. Our benchmarking results suggest that OPTIMA and OPTIMA-Overlap outperform state-of-the-art approaches in sensitivity (1.6–2× improvement) while simultaneously being more efficient (170–200%) and precise in their alignments (99% precision). These advantages are independent of the quality of the data, suggesting that our indexing approach and statistical evaluation are robust and provide improved sensitivity while guaranteeing high precision. %U https://www.biorxiv.org/content/biorxiv/early/2015/04/06/017194.full.pdf