Evidence map›Paper›PMID 21507886›Full record

ArticleNucleic acids research2011

A modified bacterial one-hybrid system yields improved quantitative models of transcription factor specificity.

Ryan G Christensen, Ankit Gupta, Zheng Zuo, Lawrence A Schriefer, Scot A Wolfe, Gary D Stormo

Abstract read
In one paragraph

Article in Nucleic acids research, 2011. 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. Review
  2. Article
  3. Article
  4. Adaptive Landscapes in the Age of Synthetic Biology.Molecular biology and evolution · 2019
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Modeling the specificity of protein-DNA interactions.Quantitative biology (Beijing, China) · 2013
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
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

6 authors.

Ryan G ChristensenDepartment of Genetics, Washington University School of Medicine, St Louis, MO 63108, USA.
Ankit Gupta
Zheng Zuo
Lawrence A Schriefer
Scot A Wolfe
Gary D Stormo

Funding

DNA PATTERN IDENTIFICATION AND ANALYSISR01HG000249 · NHGRI · WASHINGTON UNIVERSITY · PI STORMO, GARY D · 1990 to 2017
$5.6M
Systematic Analysis of Drosophila transcription factor binding specificitiesR01HG004744 · NHGRI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BRODSKY, MICHAEL H, WOLFE, SCOT A · 2008 to 2010
$1.9M
DNA-binding specificities of Cys2His2 zinc fingersR24GM078369 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2007 to 2010
$1.5M
NHGRI NIH HHS R01 HG000249NHGRI NIH HHS R01HG00249NHGRI NIH HHS R01HG004744NIGMS NIH HHS R24GM078369
6 · The paper itself

Abstract

We examine the use of high-throughput sequencing on binding sites recovered using a bacterial one-hybrid (B1H) system and find that improved models of transcription factor (TF) binding specificity can be obtained compared to standard methods of sequencing a small subset of the selected clones. We can obtain even more accurate binding models using a modified version of B1H selection method with constrained variation (CV-B1H). However, achieving these improved models using CV-B1H data required the development of a new method of analysis--GRaMS (Growth Rate Modeling of Specificity)--that estimates bacterial growth rates as a function of the quality of the recognition sequence. We benchmark these different methods of motif discovery using Zif268, a well-characterized C(2)H(2) zinc-finger TF on both a 28 bp randomized library for the standard B1H method and on 6 bp randomized library for the CV-B1H method for which 45 different experimental conditions were tested: five time points and three different IPTG and 3-AT concentrations. We find that GRaMS analysis is robust to the different experimental parameters whereas other analysis methods give widely varying results depending on the conditions of the experiment. Finally, we demonstrate that the CV-B1H assay can be performed in liquid media, which produces recognition models that are similar in quality to sequences recovered from selection on solid media.

Indexed as

Two-Hybrid System TechniquesBacteriaBinding SitesDNADNA-Binding ProteinsGene LibraryHigh-Throughput Nucleotide SequencingModels, BiologicalSequence Analysis, DNATranscription FactorsZinc FingersDNADNA-Binding ProteinsTranscription Factors

Identifiers

PMID21507886
PMCPMC3130293

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Registered trials

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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.