Evidence map›Paper›PMID 32321567›Full record

ArticleEpigenetics & chromatin2020

ATAC-seq normalization method can significantly affect differential accessibility analysis and interpretation.

Jake J Reske, Mike R Wilson, Ronald L Chandler

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

64 citing papers in PubMed, 105 citations in OpenAlex.

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

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

3 authors at 2 institutions in 1 country.

Jake J ReskeDepartment of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, 49503, USA.
Mike R WilsonDepartment of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, 49503, USA.
Ronald L ChandlerDepartment of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, 49503, USA. rlc@msu.edu.ORCID 0000-0001-5775-2594
Michigan State University · USVan Andel Institute · US

Funding

Role of chromatin remodeling and cell signaling in endometriosis etiologyR21HD099383 · NICHD · MICHIGAN STATE UNIVERSITY · PI CHANDLER, RONALD L · 2019 to 2020
$430k
Mary Kay Foundation 026-16NICHD NIH HHS R21 HD099383Ovarian Cancer Research Fund Alliance 457446
6 · The paper itself

Abstract

backgroundChromatin dysregulation is associated with developmental disorders and cancer. Numerous methods for measuring genome-wide chromatin accessibility have been developed in the genomic era to interrogate the function of chromatin regulators. A recent technique which has gained widespread use due to speed and low input requirements with native chromatin is the Assay for Transposase-Accessible Chromatin, or ATAC-seq. Biologists have since used this method to compare chromatin accessibility between two cellular conditions. However, approaches for calculating differential accessibility can yield conflicting results, and little emphasis is placed on choice of normalization method during differential ATAC-seq analysis, especially when global chromatin alterations might be expected.

resultsUsing an in vivo ATAC-seq data set generated in our recent report, we observed differences in chromatin accessibility patterns depending on the data normalization method used to calculate differential accessibility. This observation was further verified on published ATAC-seq data from yeast. We propose a generalized workflow for differential accessibility analysis using ATAC-seq data. We further show this workflow identifies sites of differential chromatin accessibility that correlate with gene expression and is sensitive to differential analysis using negative controls.

conclusionsWe argue that researchers should systematically compare multiple normalization methods before continuing with differential accessibility analysis. ATAC-seq users should be aware of the interpretations of potential bias within experimental data and the assumptions of the normalization method implemented.

Indexed as

AlgorithmsChromatinChromatin Immunoprecipitation SequencingData Interpretation, StatisticalGenome, FungalSaccharomyces cerevisiaeChromatinATAC-seqBioinformaticsChromatin accessibilityDifferential accessibilityGenomicsNormalization

Identifiers

PMID32321567
PMCPMC7178746
OpenAlexW3017630629

What OpenQuestion holds

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LicenceCC BY
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.