Evidence map›Paper›PMID 28162770›Full record

ArticleCell2017

Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras.

Tim Wang, Haiyan Yu, Nicholas W Hughes, Bingxu Liu, Arek Kendirli, Klara Klein, Walter W Chen, Eric S Lander, David M Sabatini

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

Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 397 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
397citing papers in PubMed, 1 pooled it
40.2field-weighted citation impact, top 1% 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

397 citing papers in PubMed, 1 synthesis or guideline pooled it, 684 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Changes in the transcriptome and synthetic lethal dependencies followingProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Review
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  17. KRAS Inhibition in Pancreatic Ductal Adenocarcinoma.Journal of clinical medicine · 2026
    Review
  18. Article
  19. Article
  20. Article

337 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

9 authors at 6 institutions in 2 countries.

Tim WangDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Haiyan YuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nicholas W HughesBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Bingxu LiuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Arek KendirliBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Klara KleinBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Walter W ChenDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Eric S LanderDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: lander@broadinstitute.org.
David M SabatiniDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: sabatini@wi.mit.edu.
Whitehead Institute for Biomedical Research · USBroad Institute · USAllen Institute · USGerman Cancer Research Center · DEHarvard University · USHeidelberg University · DE

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Regulation of the mTOR Pathway By NutrientsR01CA103866 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2004 to 2021
$7.0M
Improving targeted therapies through functional genomic approachesF31CA189437 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WANG, TIM · 2014 to 2017
$107k
Howard Hughes Medical InstituteNCI NIH HHS F31 CA189437NCI NIH HHS R01 CA103866NHGRI NIH HHS U54 HG003067NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) cell lines. Sets of genes with correlated patterns of essentiality across the lines reveal new gene relationships, the essential substrates of enzymes, and the molecular functions of uncharacterized proteins. Comparisons of differentially essential genes between Ras-dependent and -independent lines uncover synthetic lethal partners of oncogenic Ras. Screens in both human AML and engineered mouse pro-B cells converge on a surprisingly small number of genes in the Ras processing and MAPK pathways and pinpoint PREX1 as an AML-specific activator of MAPK signaling. Our findings suggest general strategies for defining mammalian gene networks and synthetic lethal interactions by exploiting the natural genetic and epigenetic diversity of human cancer cells.

Indexed as

Gene Regulatory NetworksAnimalsCarrier ProteinsCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsEpigenesis, GeneticGenes, EssentialHumansLeukemia, Myeloid, AcuteMAP Kinase Signaling SystemMiceMitochondrial ProteinsProtein Processing, Post-Translationalras ProteinsCarrier ProteinsCOA6 protein, humanMitochondrial Proteinsras ProteinsAMLCRISPRgene networksgenetic screensRASsynthetic lethality

Identifiers

PMID28162770
PMCPMC5445660
OpenAlexW2584033231

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.