Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Long Reads Capture Simultaneous Enhancer-Promoter Methylation Status for Cell-type Deconvolution

Sapir Margalit, Yotam Abramson, Hila Sharim, Zohar Manber, Surajit Bhattacharya, Yi-Wen Chen, Eric Vilain, Hayk Barseghyan, View ORCID ProfileRan Elkon, Roded Sharan, Yuval Ebenstein
doi: https://doi.org/10.1101/2021.01.28.428654
Sapir Margalit
1Department of physical chemistry, Tel Aviv University, Tel Aviv 6997801, Israel
2Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yotam Abramson
1Department of physical chemistry, Tel Aviv University, Tel Aviv 6997801, Israel
2Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hila Sharim
1Department of physical chemistry, Tel Aviv University, Tel Aviv 6997801, Israel
2Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zohar Manber
2Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel
3Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Surajit Bhattacharya
4Center for Genetic Medicine Research, Children’s National Hospital, 111 Michigan Avenue NW, Washington DC 20010, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yi-Wen Chen
4Center for Genetic Medicine Research, Children’s National Hospital, 111 Michigan Avenue NW, Washington DC 20010, USA
5Department of Genomics and Precision Medicine, George Washington University 1918 F Street, NW Washington, DC 20052, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric Vilain
4Center for Genetic Medicine Research, Children’s National Hospital, 111 Michigan Avenue NW, Washington DC 20010, USA
5Department of Genomics and Precision Medicine, George Washington University 1918 F Street, NW Washington, DC 20052, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hayk Barseghyan
4Center for Genetic Medicine Research, Children’s National Hospital, 111 Michigan Avenue NW, Washington DC 20010, USA
5Department of Genomics and Precision Medicine, George Washington University 1918 F Street, NW Washington, DC 20052, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ran Elkon
2Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel
3Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ran Elkon
Roded Sharan
2Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel
6School of Computer Science, Tel-Aviv University, Tel-Aviv 6997801, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: uv@post.tau.ac.il
Yuval Ebenstein
1Department of physical chemistry, Tel Aviv University, Tel Aviv 6997801, Israel
2Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: uv@post.tau.ac.il
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Motivation While promoter methylation is associated with reinforcing fundamental tissue identities, the methylation status of distant enhancers was shown by genome-wide association studies to be a powerful determinant of cell-state and cancer. With recent availability of long-reads that report on the methylation status of enhancer-promoter pairs on the same molecule, we hypothesized that probing these pairs on the single-molecule level may serve the basis for detection of rare cancerous transformations in a given cell population. We explore various analysis approaches for deconvolving cell-type mixtures based on their genome-wide enhancer-promoter methylation profiles.

Results To evaluate our hypothesis we examine long-read optical methylome data for the GM12787 cell line and myoblast cell lines from two donors. We identified over 100,000 enhancer-promoter pairs that co-exist on at least 30 individual DNA molecules per pair. We developed a detailed methodology for mixture deconvolution and applied it to estimate the proportional cell compositions in synthetic mixtures based on analyzing their enhancer-promoter pairwise methylation. We found our methodology to lead to very accurate estimates, outperforming our promoter-based deconvolutions. Moreover, we show that it can be generalized from deconvolving different cell types to subtle scenarios where one wishes to deconvolve different cell populations of the same cell-type.

Availability The code used in this work to analyze single-molecule Bionano Genomics optical maps is available via the GitHub repository https://github.com/ebensteinLab/Single_molecule_methylation_in_EP.

Contact uv{at}post.tau.ac.il (Y.E), roded{at}tauex.tau.ac.il (R.S)

Competing Interest Statement

HB and EV own a limited number of stock options of Bionano Genomics Inc. HB is also employed part-time by Bionano Genomics Inc.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted January 29, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Long Reads Capture Simultaneous Enhancer-Promoter Methylation Status for Cell-type Deconvolution
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Long Reads Capture Simultaneous Enhancer-Promoter Methylation Status for Cell-type Deconvolution
Sapir Margalit, Yotam Abramson, Hila Sharim, Zohar Manber, Surajit Bhattacharya, Yi-Wen Chen, Eric Vilain, Hayk Barseghyan, Ran Elkon, Roded Sharan, Yuval Ebenstein
bioRxiv 2021.01.28.428654; doi: https://doi.org/10.1101/2021.01.28.428654
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Long Reads Capture Simultaneous Enhancer-Promoter Methylation Status for Cell-type Deconvolution
Sapir Margalit, Yotam Abramson, Hila Sharim, Zohar Manber, Surajit Bhattacharya, Yi-Wen Chen, Eric Vilain, Hayk Barseghyan, Ran Elkon, Roded Sharan, Yuval Ebenstein
bioRxiv 2021.01.28.428654; doi: https://doi.org/10.1101/2021.01.28.428654

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Bioinformatics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4109)
  • Biochemistry (8813)
  • Bioengineering (6517)
  • Bioinformatics (23456)
  • Biophysics (11788)
  • Cancer Biology (9205)
  • Cell Biology (13318)
  • Clinical Trials (138)
  • Developmental Biology (7433)
  • Ecology (11407)
  • Epidemiology (2066)
  • Evolutionary Biology (15145)
  • Genetics (10433)
  • Genomics (14041)
  • Immunology (9169)
  • Microbiology (22152)
  • Molecular Biology (8808)
  • Neuroscience (47558)
  • Paleontology (350)
  • Pathology (1428)
  • Pharmacology and Toxicology (2491)
  • Physiology (3730)
  • Plant Biology (8079)
  • Scientific Communication and Education (1437)
  • Synthetic Biology (2220)
  • Systems Biology (6037)
  • Zoology (1252)