Evidence map›Paper›PMID 27684187›Full record

ArticleCell systems2016

Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in β-Catenin-Active Cancers.

Joseph Rosenbluh, Johnathan Mercer, Yashaswi Shrestha, Rachel Oliver, Pablo Tamayo, John G Doench, Itay Tirosh, Federica Piccioni, Ella Hartenian, Heiko Horn and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

45 citing papers in PubMed, 74 citations in OpenAlex.

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  5. Proceedings of the National Academy of Sciences of the United States of America · 2025
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  19. A new era in functional genomics screens.Nature reviews. Genetics · 2022
    Review
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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

16 authors at 5 institutions in 1 country.

Joseph RosenbluhBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA.
Johnathan MercerBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Yashaswi ShresthaBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Rachel OliverBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA.
Pablo TamayoMoores Cancer Center and School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
John G DoenchBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Itay TiroshBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Federica PiccioniBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Ella HartenianBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Heiko HornBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Lola FagbamiBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
David E RootBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Jacob JaffeBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Kasper LageBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Jesse S BoehmBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
William C HahnBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA. Electronic address: william_hahn@dfci.harvard.edu.
Broad Institute · USDana-Farber Cancer Institute · USMassachusetts General Hospital · USHarvard University · USUniversity of California, San Diego · US

Funding

Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2M
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
Knowledge-based Gene Expression Analysis for Biomedical and Cancer ResearchR01CA121941 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MESIROV, JILL P. · 2006 to 2016
$5.1M
Systematic identification of oncogenic KRAS synthetic lethal interactionsU01CA199253 · NCI · BROAD INSTITUTE, INC. · PI HAHN, WILLIAM C. · 2015 to 2019
$3.7M
GenePattern Notebooks for Cancer ResearchU24CA194107 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MESIROV, JILL P. · 2015 to 2019
$2.8M
Molecular Signatures to Characterize the Oncogenic State of Individual TumorsR01CA154480 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAMAYO, PABLO · 2011 to 2015
$2.0M
2/3 Building Integrative CNS Networks for Genomic Analysis of AutismR01MH109903 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI HANSEN, KASPER LAGE · 2016 to 2020
$1.4M
NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA121941NCI NIH HHS R01 CA154480NCI NIH HHS U01 CA176058NCI NIH HHS U01 CA199253NCI NIH HHS U24 CA194107NIMH NIH HHS R01 MH109903
6 · The paper itself

Abstract

Genome-scale expression studies and comprehensive loss-of-function genetic screens have focused almost exclusively on the highest confidence candidate genes. Here, we describe a strategy for characterizing the lower confidence candidates identified by such approaches. We interrogated 177 genes that we classified as essential for the proliferation of cancer cells exhibiting constitutive β-catenin activity and integrated data for each of the candidates, derived from orthogonal short hairpin RNA (shRNA) knockdown and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated gene editing knockout screens, to yield 69 validated genes. We then characterized the relationships between sets of these genes using complementary assays: medium-throughput stable isotope labeling by amino acids in cell culture (SILAC)-based mass spectrometry, yielding 3,639 protein-protein interactions, and a CRISPR-mediated pairwise double knockout screen, yielding 375 combinations exhibiting greater- or lesser-than-additive phenotypic effects indicating genetic interactions. These studies identify previously unreported regulators of β-catenin, define functional networks required for the survival of β-catenin-active cancers, and provide an experimental strategy that may be applied to define other signaling networks.

Indexed as

Proteomicsbeta CateninClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGene EditingGenetic TherapyHumansNeoplasmsRNA, Guide, CRISPR-Cas SystemsRNA, Small Interferingbeta CateninRNA, Guide, CRISPR-Cas SystemsRNA, Small InterferingCRISPR-Cas9genetic interactionsprotein-protein interactionsRNAiβ-catenin

Identifiers

PMID27684187
PMCPMC5455996
OpenAlexW2524692252

What OpenQuestion holds

Textmetadata
LicenceTDM
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.