Reduced representation optical methylation mapping (R2OM2).

Grunwald, A.; Sharim, H.; Gabrieli, T.; Michaeli, Y.; Torchinsky, D.; Juhasz, M.; Reifenberger, J.; Hastie, A. R.; Cao, H.; Weinhold, E.; Ebenstein, Y.

doi:10.1101/108084

bioRxiv · 10.1101/108084

Reduced representation optical methylation mapping (R2OM2).

Grunwald, A.·Sharim, H.·Gabrieli, T.·Michaeli, Y.·Torchinsky, D.·Juhasz, M.·Reifenberger, J.·Hastie, A. R.·Cao, H.·Weinhold, E.·Ebenstein, Y.

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Abstract

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.

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Grunwald, A., Sharim, H., Gabrieli, T., Michaeli, Y., Torchinsky, D., Juhasz, M., Reifenberger, J., Hastie, A. R., Cao, H., Weinhold, E., Ebenstein, Y.. 2017-03-06. Reduced representation optical methylation mapping (R2OM2).. https://doi.org/10.1101/108084

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