RT Journal Article
SR Electronic
T1 Reduced representation optical methylation mapping (R<sup>2</sup>OM<sup>2</sup>)
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 113522
DO 10.1101/113522
A1 Assaf Grunwald
A1 Hila Sharim
A1 Tslil Gabrieli
A1 Yael Michaeli
A1 Dmitry Torchinsky
A1 Matyas Juhasz
A1 Kathryn R Wagner
A1 Jonathan Pevsner
A1 Jeff Reifenberger
A1 Alex R Hastie
A1 Han Cao
A1 Elmar Weinhold
A1 Yuval Ebenstein
YR 2017
UL http://biorxiv.org/content/early/2017/03/03/113522.abstract
AB 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.