Evidence map›Paper›PMID 28764645›Full record

ArticleBMC bioinformatics2017

Correcting nucleotide-specific biases in high-throughput sequencing data.

Jeremy R Wang, Bryan Quach, Terrence S Furey

Open access · goldAbstract read
In one paragraph

Article in BMC bioinformatics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed, 26 citations in OpenAlex.

  1. Genome-wide mapping of DCP2-dependent 5' cap footprints inNAR genomics and bioinformatics · 2026
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  6. Boquila: NGS read simulator to eliminate read nucleotide bias in sequence analysis.Turkish journal of biology = Turk biyoloji dergisi · 2023
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  14. On the problem of confounders in modeling gene expression.Bioinformatics (Oxford, England) · 2019
    Review
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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

3 authors at 1 institution in 1 country.

Jeremy R WangDepartment of Genetics, University of North Carolina at Chapel Hill, CB 7032, 7314 Medical Biomolecular Research Building, 111 Mason Farm Road, Chapel Hill, 27599, NC, USA. jeremy_wang@med.unc.edu.ORCID http://orcid.org/0000-0002-0673-9418
Bryan QuachDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Terrence S FureyDepartment of Genetics, University of North Carolina at Chapel Hill, CB 7032, 7314 Medical Biomolecular Research Building, 111 Mason Farm Road, Chapel Hill, 27599, NC, USA.
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
GASTROENTEROLOGY RESEARCH TRAININGT32DK007737 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHEHZAD Z. SHEIKH · 1996 to 2026
$7.8M
UNC Predoc Training Progr in Bioinformatics/Comp BiologyT32GM067553 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ELSTON, TIMOTHY C · 2005 to 2019
$2.5M
Interpreting molecular role of DNA variants associated with Crohn's Disease through integrative analysis of open chromatin, epigenome and transcriptome data in diverse and relevant tissues and cellsR01ES024983 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FUREY, TERRENCE S., SHEIKH, SHEHZAD Z. · 2014 to 2015
$588k
NCI NIH HHS P30 CA016086NIDDK NIH HHS T32 DK007737NIEHS NIH HHS R01 ES024983NIGMS NIH HHS T32 GM067553
6 · The paper itself

Abstract

backgroundHigh-throughput sequence (HTS) data exhibit position-specific nucleotide biases that obscure the intended signal and reduce the effectiveness of these data for downstream analyses. These biases are particularly evident in HTS assays for identifying regulatory regions in DNA (DNase-seq, ChIP-seq, FAIRE-seq, ATAC-seq). Biases may result from many experiment-specific factors, including selectivity of DNA restriction enzymes and fragmentation method, as well as sequencing technology-specific factors, such as choice of adapters/primers and sample amplification methods.

resultsWe present a novel method to detect and correct position-specific nucleotide biases in HTS short read data. Our method calculates read-specific weights based on aligned reads to correct the over- or underrepresentation of position-specific nucleotide subsequences, both within and adjacent to the aligned read, relative to a baseline calculated in assay-specific enriched regions. Using HTS data from a variety of ChIP-seq, DNase-seq, FAIRE-seq, and ATAC-seq experiments, we show that our weight-adjusted reads reduce the position-specific nucleotide imbalance across reads and improve the utility of these data for downstream analyses, including identification and characterization of open chromatin peaks and transcription-factor binding sites.

conclusionsA general-purpose method to characterize and correct position-specific nucleotide sequence biases fills the need to recognize and deal with, in a systematic manner, binding-site preference for the growing number of HTS-based epigenetic assays. As the breadth and impact of these biases are better understood, the availability of a standard toolkit to correct them will be important.

Indexed as

Base SequenceBiasBinding SitesComputational BiologyDeoxyribonucleasesDNAHigh-Throughput Nucleotide SequencingNucleotidesPrincipal Component AnalysisProtein BindingSequence Analysis, DNADeoxyribonucleasesDNANucleotidesATAC-seqBias correctionChIP-seqDNase-seqEpigenomicsFAIRE-seq

Identifiers

PMID28764645
PMCPMC5540620
OpenAlexW2742088791

What OpenQuestion holds

Textmetadata
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.