Integration of Optical Maps and Short-Read Sequencing Data in Genomic Investigation

Short-read sequencing takes randomly fragmented DNA segments and retrieves the corresponding nucleobase sequence from them, yielding short sequences that can be assembled into longer contigs. Optical mapping performs a similar task, taking long DNA fragments and measuring the distances between their occurrences of specific sequence motifs to create restriction maps. Despite the similar strategy these methods employ, the data they yield is very different; short-read sequencing produces shorter and more accurate sequence-level information, while optical mapping produces much longer maps that only carry barcode-style patterns of restriction sites in the genome. While optical mapping dates back to the early 1990s and short-read sequencing to the late 1970s, it is only in the past decade that both have enjoyed notable commercial availability at the same time. As the two methods produce highly complementary data, integrating them can yield benefits where one source of data provides information the other is missing. This integration takes two forms: the creation of methods that directly use both types of data, and the creation of research environments where both types of data are well-supported. I present two tools to facilitate the latter: Rekit, an open-source optical map aligner and simulator; and a coverage browser for detecting copy number variations in Collaborative Cross mouse strains. In service of the former goal, I also present two versions of a classifier model that use short-read sequence and optical map data from the same sample to detect certain classes of structural variant in the mouse genome.