Long-read single-molecule maps of the functional methylome

Hila Sharim, Assaf Grunwald, Tslil Gabrieli, Yael Michaeli, Sapir Margalit, Dmitry Torchinsky, Rani Arielly, Gil Nifker, Matyas Juhasz, Felix Gularek, Miguel Almalvez, Brandon Dufault, Sreetama Sen Chandra, Alexander Liu, Surajit Bhattacharya, Yi Wen Chen, Eric Vilain, Kathryn R. Wagner, Jonathan Pevsner, Jeff ReifenbergerErnest T. Lam, Alex R. Hastie, Han Cao, Hayk Barseghyan, Elmar Weinhold, Yuval Ebenstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)646-656
Number of pages11
JournalGenome Research
Issue number4
StatePublished - Apr 2019


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