Evidence map›Paper›PMID 30295673›Full record

ArticleNature biotechnology2018

Nondestructive, base-resolution sequencing of 5-hydroxymethylcytosine using a DNA deaminase.

Emily K Schutsky, Jamie E DeNizio, Peng Hu, Monica Yun Liu, Christopher S Nabel, Emily B Fabyanic, Young Hwang, Frederic D Bushman, Hao Wu, Rahul M Kohli

Abstract read
In one paragraph

Article in Nature biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
8.1field-weighted citation impact, top 2% 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

113 citing papers in PubMed, 230 citations in OpenAlex.

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53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Emily K SchutskyDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID http://orcid.org/0000-0003-4885-6353
Jamie E DeNizioDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Peng HuDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Monica Yun LiuDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Christopher S NabelDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID http://orcid.org/0000-0001-6515-8579
Emily B FabyanicDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Young HwangDepartment of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Frederic D BushmanDepartment of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Hao WuDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Rahul M KohliDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID http://orcid.org/0000-0002-7689-5678
University of Pennsylvania · US

Funding

TRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM007229 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 1985 to 2023
$14.0M
Charting oxygen-sensing gene regulatory network in cardiomyocytes through single-cell analysis and epigenome editingDP2HL142044 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI WU, HAO · 2017 to 2017
$2.4M
The mechanism and modulation of 5-methylcytosine oxidation by TET family enzymesR01GM118501 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI KOHLI, RAHUL MANU · 2017 to 2020
$1.2M
Genomic and functional analysis of active DNA demethylation in mammalian cellsR00HG007982 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI WU, HAO · 2016 to 2018
$732k
APOBEC-Coupled Epigenetic SequencingR21HG009545 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI KOHLI, RAHUL MANU · 2017 to 2018
$443k
Biochemical regulation and genomic targeting of TET-catalyzed cytosine oxidationF30CA196097 · NCI · UNIVERSITY OF PENNSYLVANIA · PI LIU, MONICA YUN · 2015 to 2017
$126k
NCI NIH HHS F30 CA196097NHGRI NIH HHS R00 HG007982NHGRI NIH HHS R21 HG009545NHLBI NIH HHS DP2 HL142044NIGMS NIH HHS R01 GM118501NIGMS NIH HHS T32 GM007229
6 · The paper itself

Abstract

Here we present APOBEC-coupled epigenetic sequencing (ACE-seq), a bisulfite-free method for localizing 5-hydroxymethylcytosine (5hmC) at single-base resolution with low DNA input. The method builds on the observation that AID/APOBEC family DNA deaminase enzymes can potently discriminate between cytosine modification states and exploits the non-destructive nature of enzymatic, rather than chemical, deamination. ACE-seq yielded high-confidence 5hmC profiles with at least 1,000-fold less DNA input than conventional methods. Applying ACE-seq to generate a base-resolution map of 5hmC in tissue-derived cortical excitatory neurons, we found that 5hmC was almost entirely confined to CG dinucleotides. The whole-genome map permitted cytosine, 5-methylcytosine (5mC) and 5hmC to be parsed and revealed genomic features that diverged from global patterns, including enhancers and imprinting control regions with high and low 5hmC/5mC ratios, respectively. Enzymatic deamination overcomes many challenges posed by bisulfite-based methods, thus expanding the scope of epigenome profiling to include scarce samples and opening new lines of inquiry regarding the role of cytosine modifications in genome biology.

Identifiers

PMID30295673
PMCPMC6453757
OpenAlexW2895076946

What OpenQuestion holds

Textmetadata
LicenceTDM
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.