Evidence map›Paper›PMID 24104479›Full record

ArticleMolecular systems biology2013

A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities.

Franco J Vizeacoumar, Roland Arnold, Frederick S Vizeacoumar, Megha Chandrashekhar, Alla Buzina, Jordan T F Young, Julian H M Kwan, Azin Sayad, Patricia Mero, Steffen Lawo and 22 more

Open access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
4.6field-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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

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  19. G2G: A web-server for the prediction of human synthetic lethal interactions.Computational and structural biotechnology journal · 2020
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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

32 authors at 9 institutions in 2 countries.

Franco J Vizeacoumar1] Donnelly Centre and Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada [2] Saskatchewan Cancer Agency, Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Roland Arnold
Frederick S Vizeacoumar
Megha Chandrashekhar
Alla Buzina
Jordan T F Young
Julian H M Kwan
Azin Sayad
Patricia Mero
Steffen Lawo
Hiromasa Tanaka
Kevin R Brown
Anastasia Baryshnikova
Anthony B Mak
Yaroslav Fedyshyn
Yadong Wang
Glauber C Brito
Dahlia Kasimer
Taras Makhnevych
Troy Ketela
Alessandro Datti
Mohan Babu
Andrew Emili
Laurence Pelletier
Jeff Wrana
Zev Wainberg
Philip M Kim
Robert Rottapel
Catherine A O'Brien
Brenda Andrews
Charles Boone
Jason Moffat
University of Toronto · CALunenfeld-Tanenbaum Research Institute · CAMount Sinai Hospital · CAPrincess Margaret Cancer Centre · CAOntario Institute for Cancer Research · CASaskatchewan Cancer Agency · CAUniversity of California, Los Angeles · USUniversity of Regina · CAUniversity of Saskatchewan · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Improved efforts are necessary to define the functional product of cancer mutations currently being revealed through large-scale sequencing efforts. Using genome-scale pooled shRNA screening technology, we mapped negative genetic interactions across a set of isogenic cancer cell lines and confirmed hundreds of these interactions in orthogonal co-culture competition assays to generate a high-confidence genetic interaction network of differentially essential or differential essentiality (DiE) genes. The network uncovered examples of conserved genetic interactions, densely connected functional modules derived from comparative genomics with model systems data, functions for uncharacterized genes in the human genome and targetable vulnerabilities. Finally, we demonstrate a general applicability of DiE gene signatures in determining genetic dependencies of other non-isogenic cancer cell lines. For example, the PTEN(-/-) DiE genes reveal a signature that can preferentially classify PTEN-dependent genotypes across a series of non-isogenic cell lines derived from the breast, pancreas and ovarian cancers. Our reference network suggests that many cancer vulnerabilities remain to be discovered through systematic derivation of a network of differentially essential genes in an isogenic cancer cell model.

Indexed as

Epistasis, GeneticGenes, EssentialBreast NeoplasmsCell Line, TumorCoculture TechniquesFemaleGene Regulatory NetworksGenome, HumanHumansMutationNeoplasm ProteinsOvarian NeoplasmsPancreatic NeoplasmsPTEN PhosphohydrolaseRNA, Small InterferingNeoplasm ProteinsPTEN PhosphohydrolasePTEN protein, humanRNA, Small Interfering

Identifiers

PMID24104479
PMCPMC3817404
OpenAlexW2029346055

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.