Long-read single-molecule maps of the functional methylome

Authors

Hila Sharim, Tel Aviv University
Assaf Grunwald, Tel Aviv University
Tslil Gabrieli, Tel Aviv University
Yael Michaeli, Tel Aviv University
Sapir Margalit, Tel Aviv University
Dmitry Torchinsky, Tel Aviv University
Rani Arielly, Tel Aviv University
Gil Nifker, Tel Aviv University
Matyas Juhasz, Rheinisch-Westfälische Technische Hochschule Aachen
Felix Gularek, Rheinisch-Westfälische Technische Hochschule Aachen
Miguel Almalvez, Childrens National Health System
Brandon Dufault, Childrens National Health System
Sreetama Sen Chandra, Childrens National Health System
Alexander Liu, Childrens National Health System
Surajit Bhattacharya, Childrens National Health System
Yi Wen Chen, Childrens National Health System
Eric Vilain, Childrens National Health System
Kathryn R. Wagner, Johns Hopkins School of Medicine
Jonathan Pevsner, Johns Hopkins School of Medicine
Jeff Reifenberger, Bionano Genomics, Inc.
Ernest T. Lam, Bionano Genomics, Inc.
Alex R. Hastie, Bionano Genomics, Inc.
Han Cao, Bionano Genomics, Inc.
Hayk Barseghyan, Childrens National Health System
Elmar Weinhold, Rheinisch-Westfälische Technische Hochschule Aachen
Yuval Ebenstein, Tel Aviv University

Document Type

Journal Article

Publication Date

4-1-2019

Journal

Genome Research

Volume

29

Issue

4

DOI

10.1101/gr.240739.118

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.

APA Citation

Sharim, H., Grunwald, A., Gabrieli, T., Michaeli, Y., Margalit, S., Torchinsky, D., Arielly, R., Nifker, G., Juhasz, M., Gularek, F., Almalvez, M., Dufault, B., Chandra, S., Liu, A., Bhattacharya, S., Chen, Y., Vilain, E., Wagner, K., Pevsner, J., Reifenberger, J., Lam, E., Hastie, A., Cao, H., Barseghyan, H., Weinhold, E., & Ebenstein, Y. (2019). Long-read single-molecule maps of the functional methylome. Genome Research, 29 (4). http://dx.doi.org/10.1101/gr.240739.118