학술논문
Long-read single-molecule maps of the functional methylome.
Document Type
article
Author
Sharim, Hila; Grunwald, Assaf; Gabrieli, Tslil; Michaeli, Yael; Margalit, Sapir; Torchinsky, Dmitry; Arielly, Rani; Nifker, Gil; Juhasz, Matyas; Gularek, Felix; Almalvez, Miguel; Dufault, Brandon; Chandra, Sreetama; Liu, Alexander; Bhattacharya, Surajit; Chen, Yi-Wen; Vilain, Eric; Wagner, Kathryn; Pevsner, Jonathan; Reifenberger, Jeff; Lam, Ernest; Hastie, Alex; Cao, Han; Barseghyan, Hayk; Weinhold, Elmar; Ebenstein, Yuval
Source
Genome Research. 29(4)
Subject
Language
Abstract
We report on the development of a methylation analysis workflow for optical detection of fluorescent methylation profiles along chromosomal DNA molecules. In combination with Bionano Genomics genome mapping technology, these profiles provide a hybrid genetic/epigenetic genome-wide map composed of DNA molecules spanning hundreds of kilobase pairs. The method provides kilobase pair-scale genomic methylation patterns comparable to whole-genome bisulfite sequencing (WGBS) along genes and regulatory elements. These long single-molecule reads allow for methylation variation calling and analysis of large structural aberrations such as pathogenic macrosatellite arrays not accessible to single-cell second-generation sequencing. The method is applied here to study facioscapulohumeral muscular dystrophy (FSHD), simultaneously recording the haplotype, copy number, and methylation status of the disease-associated, highly repetitive locus on Chromosome 4q.