Evidence map›Paper›PMID 26472758›Full record

ArticleScience (New York, N.Y.)2015

Identification and characterization of essential genes in the human genome.

Tim Wang, Kıvanç Birsoy, Nicholas W Hughes, Kevin M Krupczak, Yorick Post, Jenny J Wei, Eric S Lander, David M Sabatini

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,010 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,010citing papers in PubMed, 1 pooled it
81.6field-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

1,010 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,761 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  10. Loss of U11/U12 spliceosome geneLife science alliance · 2026
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950 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 1 country.

Tim WangDepartment of Biology, Massachusetts Institute of Technology, Cambridge MA 02139, USA. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
Kıvanç BirsoyDepartment of Biology, Massachusetts Institute of Technology, Cambridge MA 02139, USA. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
Nicholas W HughesBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
Kevin M KrupczakWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
Yorick PostWhitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
Jenny J WeiDepartment of Biology, Massachusetts Institute of Technology, Cambridge MA 02139, USA. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Eric S LanderDepartment of Biology, Massachusetts Institute of Technology, Cambridge MA 02139, USA. Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. lander@broadinstitute.org sabatini@wi.mit.edu.
David M SabatiniDepartment of Biology, Massachusetts Institute of Technology, Cambridge MA 02139, USA. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Broad Institute of MIT and Harvard, 7 Cambridge Center, 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. lander@broadinstitute.org sabatini@wi.mit.edu.
Allen Institute · USWhitehead Institute for Biomedical Research · USBroad Institute · USHarvard University · USMassachusetts Institute of Technology · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
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 CA103866NCI NIH HHS F31 CA189437NCI NIH HHS P30 CA014051NCI NIH HHS R01 CA103866NHGRI NIH HHS 2U54HG003067-10NHGRI NIH HHS U54 HG003067NIGMS NIH HHS T32 GM007287
6 · The paper itself

Abstract

Large-scale genetic analysis of lethal phenotypes has elucidated the molecular underpinnings of many biological processes. Using the bacterial clustered regularly interspaced short palindromic repeats (CRISPR) system, we constructed a genome-wide single-guide RNA library to screen for genes required for proliferation and survival in a human cancer cell line. Our screen revealed the set of cell-essential genes, which was validated with an orthogonal gene-trap-based screen and comparison with yeast gene knockouts. This set is enriched for genes that encode components of fundamental pathways, are expressed at high levels, and contain few inactivating polymorphisms in the human population. We also uncovered a large group of uncharacterized genes involved in RNA processing, a number of whose products localize to the nucleolus. Last, screens in additional cell lines showed a high degree of overlap in gene essentiality but also revealed differences specific to each cell line and cancer type that reflect the developmental origin, oncogenic drivers, paralogous gene expression pattern, and chromosomal structure of each line. These results demonstrate the power of CRISPR-based screens and suggest a general strategy for identifying liabilities in cancer cells.

Indexed as

Genes, EssentialCell Line, TumorCell NucleolusCRISPR-Cas SystemsGene Expression ProfilingGene Knockout TechniquesGenetic TestingGenome, HumanGenomic LibraryHumansNeoplasmsRNA, Guide, CRISPR-Cas SystemsRNA Processing, Post-TranscriptionalRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID26472758
PMCPMC4662922
OpenAlexW1934704664

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.