Evidence map›Paper›PMID 25010907›Full record

ArticleNature protocols2014

Quantitative analysis of triple-mutant genetic interactions.

Hannes Braberg, Richard Alexander, Michael Shales, Jiewei Xu, Kathleen E Franks-Skiba, Qiuqin Wu, James E Haber, Nevan J Krogan

Abstract read
In one paragraph

Article in Nature protocols, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Mutation Edgotype Drives Fitness Effect in Human.Frontiers in bioinformatics · 2021
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. 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

8 authors.

Hannes Braberg1] Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA. [2] California Institute for Quantitative Biosciences (QB3), San Francisco, California, USA.
Richard Alexander1] Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA. [2] California Institute for Quantitative Biosciences (QB3), San Francisco, California, USA.
Michael Shales1] Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA. [2] California Institute for Quantitative Biosciences (QB3), San Francisco, California, USA.
Jiewei Xu1] Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA. [2] California Institute for Quantitative Biosciences (QB3), San Francisco, California, USA.
Kathleen E Franks-Skiba1] Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA. [2] California Institute for Quantitative Biosciences (QB3), San Francisco, California, USA.
Qiuqin WuDepartment of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts, USA.
James E HaberDepartment of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts, USA.
Nevan J Krogan1] Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA. [2] California Institute for Quantitative Biosciences (QB3), San Francisco, California, USA. [3] J. David Gladstone Institutes, San Francisco, California, USA.

Funding

Rewiring Therapeutic Cells: User-Controlled T Cells and Stem CellsP50GM081879 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2010 to 2017
$19.0M
Recombination Mechanisms in Yeast Cell DifferentiationR37GM020056 · NIGMS · BRANDEIS UNIVERSITY · PI HABER, JAMES E · 2007 to 2016
$5.5M
Arrest, Recovery, and Adaptation from DNA DamageR01GM061766 · NIGMS · BRANDEIS UNIVERSITY · PI HABER, JAMES E · 2001 to 2016
$4.6M
Comparative Analysis of Genetic Interaction NetworksR01GM084279 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY, KROGAN, NEVAN J · 2008 to 2017
$3.9M
Analysis of Break-Induced ReplicationR01GM076020 · NIGMS · BRANDEIS UNIVERSITY · PI HABER, JAMES E · 2006 to 2017
$3.4M
RECOMBINATION MECHANISMS IN YEAST CELL DIFFERENTIATIONR01GM020056 · NIGMS · BRANDEIS UNIVERSITY · PI HABER, JAMES E · 1985 to 2006
$3.4M
Genetic Analysis of the Nucleosome and RNA Polymerase II: A Systems ApproachR01GM084448 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2008 to 2012
$2.3M
Integrating computation and genetics to quantify specificity in protein networksR01GM098101 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA, KROGAN, NEVAN J · 2011 to 2014
$1.7M
NIGMS NIH HHS GM081879NIGMS NIH HHS GM084279NIGMS NIH HHS GM084448NIGMS NIH HHS GM098101NIGMS NIH HHS GM20056NIGMS NIH HHS GM61766NIGMS NIH HHS GM76020NIGMS NIH HHS P50 GM081879NIGMS NIH HHS R01 GM020056NIGMS NIH HHS R01 GM061766NIGMS NIH HHS R01 GM076020NIGMS NIH HHS R01 GM084279NIGMS NIH HHS R01 GM084448NIGMS NIH HHS R01 GM098101NIGMS NIH HHS R37 GM020056
6 · The paper itself

Abstract

The quantitative analysis of genetic interactions between pairs of gene mutations has proven to be effective for characterizing cellular functions, but it can miss important interactions for functionally redundant genes. To address this limitation, we have developed an approach termed triple-mutant analysis (TMA). The procedure relies on a query strain that contains two deletions in a pair of redundant or otherwise related genes, which is crossed against a panel of candidate deletion strains to isolate triple mutants and measure their growth. A central feature of TMA is to interrogate mutants that are synthetically sick when two other genes are deleted but interact minimally with either single deletion. This approach has been valuable for discovering genes that restore critical functions when the principal actors are deleted. TMA has also uncovered double-mutant combinations that produce severe defects because a third protein becomes deregulated and acts in a deleterious fashion, and it has revealed functional differences between proteins presumed to act together. The protocol is optimized for Singer ROTOR pinning robots, takes 3 weeks to complete and measures interactions for up to 30 double mutants against a library of 1,536 single mutants.

Indexed as

Gene DeletionGene Regulatory NetworksGenesGenetic Association StudiesSaccharomyces cerevisiaeSchizosaccharomyces

Identifiers

PMID25010907
PMCPMC4167031

What OpenQuestion holds

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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.