Evidence map›Paper›PMID 31932773›Full record

ArticleNature protocols2020

Multi-contact 4C: long-molecule sequencing of complex proximity ligation products to uncover local cooperative and competitive chromatin topologies.

Carlo Vermeulen, Amin Allahyar, Britta A M Bouwman, Peter H L Krijger, Marjon J A M Verstegen, Geert Geeven, Christian Valdes-Quezada, Ivo Renkens, Roy Straver, Wigard P Kloosterman and 2 more

Abstract read
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In one paragraph

Article in Nature protocols, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

21 citing papers in PubMed, 36 citations in OpenAlex.

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  12. Capturing Chromosome Conformation Across Length Scales.Journal of visualized experiments : JoVE · 2023
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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

12 authors at 2 institutions in 1 country.

Carlo Vermeulen *Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-0412-5313
Amin Allahyar *Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-2567-0273
Britta A M BouwmanOncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0002-9827-9497
Peter H L KrijgerOncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-1702-348X
Marjon J A M VerstegenOncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.
Geert GeevenOncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0002-5603-0095
Christian Valdes-QuezadaOncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0001-6790-8601
Ivo RenkensOncode Institute, Center for Molecular Medicine, University Medical Center, Utrecht University, Utrecht, the Netherlands.
Roy StraverOncode Institute, Center for Molecular Medicine, University Medical Center, Utrecht University, Utrecht, the Netherlands.
Wigard P KloostermanOncode Institute, Center for Molecular Medicine, University Medical Center, Utrecht University, Utrecht, the Netherlands.ORCID http://orcid.org/0000-0003-3357-4580
Jeroen de RidderOncode Institute, Center for Molecular Medicine, University Medical Center, Utrecht University, Utrecht, the Netherlands. j.deridder-4@umcutrecht.nl.ORCID http://orcid.org/0000-0002-0828-3477
Wouter de LaatOncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands. w.delaat@hubrecht.eu.ORCID http://orcid.org/0000-0002-6393-595X
University Medical Center Utrecht · NLUtrecht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We present the experimental protocol and data analysis toolbox for multi-contact 4C (MC-4C), a new proximity ligation method tailored to study the higher-order chromatin contact patterns of selected genomic sites. Conventional chromatin conformation capture (3C) methods fragment proximity ligation products for efficient analysis of pairwise DNA contacts. By contrast, MC-4C is designed to preserve and collect large concatemers of proximity ligated fragments for long-molecule sequencing on an Oxford Nanopore or Pacific Biosciences platform. Each concatemer of proximity ligation products represents a snapshot topology of a different individual allele, revealing its multi-way chromatin interactions. By inverse PCR with primers specific for a fragment of interest (the viewpoint) and DNA size selection, sequencing is selectively targeted to thousands of different complex interactions containing this viewpoint. A tailored statistical analysis toolbox is able to generate background models and three-way interaction profiles from the same dataset. These profiles can be used to distinguish whether contacts between more than two regulatory sequences are mutually exclusive or, conversely, simultaneously occurring at chromatin hubs. The entire procedure can be completed in 2 w, and requires standard molecular biology and data analysis skills and equipment, plus access to a third-generation sequencing platform.

Indexed as

ChromatinHumansK562 CellsMolecular ConformationSequence Analysis, DNAChromatin

Identifiers

PMID31932773
OpenAlexW3000342766

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.