TY - JOUR T1 - Reduced representation optical methylation mapping (R<sup>2</sup>OM<sup>2</sup>) JF - bioRxiv DO - 10.1101/108084 SP - 108084 AU - Assaf Grunwald AU - Hila Sharim AU - Tslil Gabrieli AU - Yael Michaeli AU - Dmitry Torchinsky AU - Matyas Juhasz AU - Kathryn R Wagner AU - Jonathan Pevsner AU - Jeff Reifenberger AU - Alex R Hastie AU - Han Cao AU - Elmar Weinhold AU - Yuval Ebenstein Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/06/108084.abstract N2 - Reduced representation methylation profiling is a method of analysis in which a subset of CpGs is used to report the overall methylation status of the probed genomic regions. This approach has been widely adopted for genome-scale bisulfite sequencing since it requires fewer sequencing reads and uses significantly less starting material than whole-genome analysis. Consequently, this method is suitable for profiling medical samples and single cells at high throughput and reduced costs. Here, we use this concept in order to create a pattern of fluorescent optical methylation profiles along individual DNA molecules. Reduced representation optical methylation mapping (R2OM2) in combination with Bionano Genomics next generation genome mapping (NGM) technology provides a hybrid genetic/epigenetic genome map of individual chromosome segments spanning hundreds of kilobase pairs (kbp). These long reads, along with the single-molecule resolution, allow for epigenetic variation calling and methylation analysis of large structural aberrations such as pathogenic macrosatellite arrays not accessible to single-cell next generation sequencing (NGS). We apply this method to facioscapulohumeral dystrophy (FSHD) showing both structural variation and hypomethylation status of a disease-associated, highly repetitive locus on chromosome 4q. ER -