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Simultaneous profiling of chromatin accessibility and methylation on human cell lines with nanopore sequencing

Isac Lee, Roham Razaghi, Timothy Gilpatrick, Michael Molnar, Norah Sadowski, Jared T. Simpson, View ORCID ProfileFritz J. Sedlazeck, View ORCID ProfileWinston Timp
doi: https://doi.org/10.1101/504993
Isac Lee
1Johns Hopkins University Department of Biomedical Engineering
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Roham Razaghi
1Johns Hopkins University Department of Biomedical Engineering
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Timothy Gilpatrick
1Johns Hopkins University Department of Biomedical Engineering
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Michael Molnar
2Ontario Institute for Cancer Research, Toronto, Ontario, Canada
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Norah Sadowski
1Johns Hopkins University Department of Biomedical Engineering
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Jared T. Simpson
2Ontario Institute for Cancer Research, Toronto, Ontario, Canada
4University of Toronto Department of Computer Science
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Fritz J. Sedlazeck
3Human Genome Sequencing Center, Baylor College of Medicine
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  • ORCID record for Fritz J. Sedlazeck
Winston Timp
1Johns Hopkins University Department of Biomedical Engineering
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  • ORCID record for Winston Timp
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ABSTRACT

Understanding how the genome and the epigenome work together to control gene transcription has applications in our understanding of diseases such as human cancer. In this study, we combine the ability of NOMe-seq to simultaneously evaluate CpG methylation and chromatin accessibility, with long-read nanopore sequencing technology, a method we call nanoNOMe. We generated >60Gb whole-genome nanopore sequencing data for each of four human cell lines (GM12878, MCF-10A, MCF-7, MDA-MB-231) including repetitive regions inaccessible by short read sequencing. Using the long reads, we find that we can observe phased methylation and chromatin accessibility, large scale pattern changes, and genetic changes such as structural variations from a single assay.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 02, 2019.
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Simultaneous profiling of chromatin accessibility and methylation on human cell lines with nanopore sequencing
Isac Lee, Roham Razaghi, Timothy Gilpatrick, Michael Molnar, Norah Sadowski, Jared T. Simpson, Fritz J. Sedlazeck, Winston Timp
bioRxiv 504993; doi: https://doi.org/10.1101/504993
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Simultaneous profiling of chromatin accessibility and methylation on human cell lines with nanopore sequencing
Isac Lee, Roham Razaghi, Timothy Gilpatrick, Michael Molnar, Norah Sadowski, Jared T. Simpson, Fritz J. Sedlazeck, Winston Timp
bioRxiv 504993; doi: https://doi.org/10.1101/504993

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