RESUMEN
Optical mapping (OM) provides single-molecule readouts of fluorescently labeled sequence motifs on long fragments of DNA, resolved to nucleotide-level coordinates. With the advent of microfluidic technologies for analysis of DNA molecules, it is possible to inexpensively generate long OM data ( > 150 kbp) at high coverage. In addition to scaffolding for de novo assembly, OM data can be aligned to a reference genome for identification of genomic structural variants. We introduce FaNDOM (Fast Nested Distance Seeding of Optical Maps)-an optical map alignment tool that greatly reduces the search space of the alignment process. On four benchmark human datasets, FaNDOM was significantly (4-14×) faster than competing tools while maintaining comparable sensitivity and specificity. We used FaNDOM to map variants in three cancer cell lines and identified many biologically interesting structural variants, including deletions, duplications, gene fusions and gene-disrupting rearrangements. FaNDOM is publicly available at https://github.com/jluebeck/FaNDOM.