Evidence map›Paper›PMID 33958785›Full record

ArticleNature biotechnology2021

Extended-representation bisulfite sequencing of gene regulatory elements in multiplexed samples and single cells.

Sarah J Shareef, Samantha M Bevill, Ayush T Raman, Martin J Aryee, Peter van Galen, Volker Hovestadt, Bradley E Bernstein

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
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  8. Article
  9. Article
  10. DNA Methylation in Rice: Mechanisms, Regulatory Roles, and Beyond.International journal of molecular sciences · 2025
    Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Biomarkers of aging.Science China. Life sciences · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Sarah J ShareefDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Samantha M BevillDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Ayush T RamanDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Martin J AryeeDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6848-1344
Peter van GalenDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0735-1570
Volker HovestadtDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. volker_hovestadt@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-3480-6649
Bradley E BernsteinDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. bernstein.bradley@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-5726-6278
Broad Institute · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Epigenetic plasticity in tumor initiation and evolutionDP1CA216873 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BERNSTEIN, BRADLEY EVAN · 2016 to 2020
$5.9M
Human Frontier Science Program (HFSP) LT000596/2016-LNCI NIH HHS DP1 CA216873NIGMS NIH HHS T32 GM007753U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) DP1CA216873U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM007753
6 · The paper itself

Abstract

The biological roles of DNA methylation have been elucidated by profiling methods based on whole-genome or reduced-representation bisulfite sequencing, but these approaches do not efficiently survey the vast numbers of non-coding regulatory elements in mammalian genomes. Here we present an extended-representation bisulfite sequencing (XRBS) method for targeted profiling of DNA methylation. Our design strikes a balance between expanding coverage of regulatory elements and reproducibly enriching informative CpG dinucleotides in promoters, enhancers and CTCF binding sites. Barcoded DNA fragments are pooled before bisulfite conversion, allowing multiplex processing and technical consistency in low-input samples. Application of XRBS to single leukemia cells enabled us to evaluate genetic copy number variations and methylation variability across individual cells. Our analysis highlights heterochromatic H3K9me3 regions as having the highest cell-to-cell variability in their methylation, likely reflecting inherent epigenetic instability of these late-replicating regions, compounded by differences in cell cycle stages among sampled cells.

Indexed as

Gene Regulatory NetworksHigh-Throughput Nucleotide SequencingCpG IslandsDNA MethylationHistonesHumansSingle-Cell AnalysisSulfitesHistonesSulfites

Identifiers

PMID33958785
PMCPMC8434949
OpenAlexW3157044858

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.