Evidence map›Paper›PMID 29778836›Full record

ArticleCell systems2018

Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens.

Joshua Pan, Robin M Meyers, Brittany C Michel, Nazar Mashtalir, Ann E Sizemore, Jonathan N Wells, Seth H Cassel, Francisca Vazquez, Barbara A Weir, William C Hahn and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.

0numbers the graph read from it
0cells of the map it votes in
108citing 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

108 citing papers in PubMed.

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  16. Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Article
  18. Article
  19. A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis.The Journal of experimental medicine · 2025
    Article
  20. Review

48 more citing papers are in PubMed but not listed here.

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

13 authors.

Joshua PanDana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Biomedical and Biological Sciences Program, Harvard Medical School, Boston, MA 02115, USA.
Robin M MeyersBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Brittany C MichelDana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Biomedical and Biological Sciences Program, Harvard Medical School, Boston, MA 02115, USA.
Nazar MashtalirDana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Ann E SizemoreBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Jonathan N WellsMRC Human Genetics Unit, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Seth H CasselDana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Biomedical and Biological Sciences Program, Harvard Medical School, Boston, MA 02115, USA; Medical Scientist Training Program, Harvard Medical School, Boston, MA 02115, USA.
Francisca VazquezBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Barbara A WeirBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
William C HahnDana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Joseph A MarshMRC Human Genetics Unit, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Aviad TsherniakBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Cigall KadochDana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: cigall_kadoch@dfci.harvard.edu.

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
The Dana-Farber Cancer Institute Cancer Target Discovery and Development CenterU01CA176058 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2013 to 2021
$7.8M
Reversing Oncogenic BAF Complex Structure & Function: New Therapeutic ApproachesDP2CA195762 · NCI · DANA-FARBER CANCER INST · PI KADOCH, CIGALL · 2014 to 2014
$2.6M
Genetics and Genomics PhD Training GrantT32GM096911 · NIGMS · HARVARD MEDICAL SCHOOL · PI KENNEDY, SCOTT G · 2011 to 2020
$2.5M
Medical Research Council MR/M02122X/1NCI NIH HHS DP2 CA195762NCI NIH HHS U01 CA176058NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM096911
6 · The paper itself

Abstract

Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks that recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex. Finally, by integrating functional networks with large protein-protein interaction networks, we discovered novel protein complexes involving recently evolved genes of unknown function. Taken together, these findings demonstrate the utility of genetic perturbation screens alone, and in combination with large-scale biophysical data, to enhance our understanding of mammalian protein complexes in normal and disease states.

Indexed as

A549 CellsAnimalsCell Line, TumorCRISPR-Cas SystemsGenes, EssentialGenetic FitnessGenetic TestingHEK293 CellsHumansMammalsMultiprotein ComplexesProtein Interaction MappingProtein Interaction MapsRNA InterferenceMultiprotein Complexesfitness correlationsgenetic perturbation screensmammalian SWI/SNFprotein complexesshRNA and CRISPR/Cas9-based genetic screens

Identifiers

PMID29778836
PMCPMC6152908

What OpenQuestion holds

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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.