Evidence map›Paper›PMID 29672735›Full record

ArticleNucleic acids research2018

Parallel factor ChIP provides essential internal control for quantitative differential ChIP-seq.

Michael J Guertin, Amy E Cullen, Florian Markowetz, Andrew N Holding

Abstract read
In one paragraph

Article in Nucleic acids research, 2018. 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
–field-weighted citation impact
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.

  1. Article
  2. Review
  3. Article
  4. Article
  5. The Wild West of spike-in normalization.Nature biotechnology · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. CBP Is Required for Establishing Adaptive Gene Programs in the Adult Mouse Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
    Article
  11. Article
  12. A new approach for quantifying epigenetic landscapes.The Journal of biological chemistry · 2020
    Article
  13. Article
  14. Article
  15. Article
  16. Article
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  18. Article
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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

4 authors.

Michael J GuertinDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Amy E CullenCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, Cambridgeshire CB2 0RE, UK.
Florian MarkowetzCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, Cambridgeshire CB2 0RE, UK.
Andrew N HoldingCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, Cambridgeshire CB2 0RE, UK.

Funding

Cancer Research UK 19274Cancer Research UK 24631
6 · The paper itself

Abstract

A key challenge in quantitative ChIP combined with high-throughput sequencing (ChIP-seq) is the normalization of data in the presence of genome-wide changes in occupancy. Analysis-based normalization methods were developed for transcriptomic data and these are dependent on the underlying assumption that total transcription does not change between conditions. For genome-wide changes in transcription factor (TF) binding, these assumptions do not hold true. The challenges in normalization are confounded by experimental variability during sample preparation, processing and recovery. We present a novel normalization strategy utilizing an internal standard of unchanged peaks for reference. Our method can be readily applied to monitor genome-wide changes by ChIP-seq that are otherwise lost or misrepresented through analytical normalization. We compare our approach to normalization by total read depth and two alternative methods that utilize external experimental controls to study TF binding. We successfully resolve the key challenges in quantitative ChIP-seq analysis and demonstrate its application by monitoring the loss of Estrogen Receptor-alpha (ER) binding upon fulvestrant treatment, ER binding in response to estrodiol, ER mediated change in H4K12 acetylation and profiling ER binding in patient-derived xenographs. This is supported by an adaptable pipeline to normalize and quantify differential TF binding genome-wide and generate metrics for differential binding at individual sites.

Indexed as

AnimalsAntibodiesCCCTC-Binding FactorChromatin ImmunoprecipitationDrosophila melanogasterEstrogen Receptor alphaHigh-Throughput Nucleotide SequencingHistonesHumansMCF-7 CellsMiceReference StandardsSequence Analysis, DNAAntibodiesCCCTC-Binding FactorEstrogen Receptor alphaHistones

Identifiers

PMID29672735
PMCPMC6093181

What OpenQuestion holds

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LicenceCC BY
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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.