Identification and characterization of essential genes in the human genome

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

doi:10.1126/science.aac7041

Cited by 1,617CRISPR and Genetic EngineeringChromatin Remodeling and CancerCancer Genomics and Diagnostics

Identification and characterization of essential genes in the human genome

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Wang, Tim, Birsoy, Kıvanç, Hughes, Nicholas W., Krupczak, Kevin M., Post, Yorick, Wei, Jenny J., Lander, Eric S., Sabatini, David M.·2015·Science

DOI 10.1126/science.aac7041PMC PMC4662922

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Abstract

Zeroing in on essential human genes: More powerful genetic techniques are helping to define the list of genes required for the life of a human cell. Two papers used the CRISPR genome editing system and a gene trap method in haploid human cells to screen for essential genes (see the Perspective by Boone and Andrews). Wang et al. 's analysis of multiple cell lines indicates that it may be possible to find tumor-specific dependencies on particular genes. Blomen et al. investigate the phenomenon in which nonessential genes are required for fitness in the absence of another gene. Hence, complexity rather than robustness is the human strategy. Science , this issue p. 1096 and p. 1092 ; see also p. 1028

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Pooled CRISPR screening is a powerful and widely used method for identifying genes involved in biological mechanisms such as cell proliferation, drug resistance, and viral infection.
“Pooled CRISPR screening is a powerful and widely used method for identifying genes involved in biological mechanisms such as cell proliferation 1, 2 , drug resistance 3 , and viral infection 4 .”
From Pooled CRISPR screening with single-cell transcriptome readout. (2017) · cites this paper as [2]
Joung, J.'s team employed the SHERLOCK technique to detect SARS-CoV-2 viral RNA using the CRISPR-Cas13a system.
“Joung, J.'s team employed the SHERLOCK technique to detect SARS-CoV-2 viral RNA using the CRISPR-Cas13a system.”
From A Review of Research on CRISPR/Cas9 Gene Editing Technology in Disease Treatment (2024) · cites this paper as [17]
The paper’s Abstract describes CRISPR-Cas9 and gene-trap screens for essential genes in human cells. Searches for Joung, SHERLOCK, SARS-CoV-2, Cas13a, and viral RNA detection found no passage addressing the claimed diagnostic technique. (LLM, conf=0.78)
Experimental — accuracy not yet measured
This assay is highly sensitive and specific, capable of detecting low concentrations of SARS-CoV-2 RNA in a short period of time.
“This assay is highly sensitive and specific, capable of detecting low concentrations of SARS-CoV-2 RNA in a short period of time [17].”
From A Review of Research on CRISPR/Cas9 Gene Editing Technology in Disease Treatment (2024) · cites this paper as [17]
The paper’s indexed Abstract describes CRISPR and gene-trap screens for genes essential to human cancer-cell survival, not a viral RNA detection assay. Searches for SARS-CoV-2 RNA and for rapid, sensitive diagnostic detection found no passage addressing the assay’s sensitivity, specificity, detection limit, or speed. No page number is provided for the indexed passages. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Many identified mediator complex components were concordantly associated with resistance to other targeted cancer therapies, but were also controversially identified as essential genes in CML cells.
“Many of the identified mediator complex components were concordantly associated with resistance to other targeted cancer therapies,44,45 but were also controversially identified as essential genes in CML cells.46”
From Integrated drug profiling and CRISPR screening identify BCR::ABL1-independent vulnerabilities in chronic myeloid leukemia (2024) · cites this paper as [46]
The passage labeled Abstract (page unavailable) reports screens in CML cell lines and identifies CML-essential genes, but it does not identify Mediator complex components among them. Searches for “Mediator complex” and MED subunit names found no passage in our copy establishing the specific claim attributed to citation 46; the resistance-to-therapy clause is attached to citations 44 and 45, not this source. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Gene-level enrichment scores were highly correlated with a previous genome-wide CRISPR screen in K562 cells (r = 0.85).
“we computed gene-level enrichment scores (Supplementary Fig. 4e, Supplementary Table 3), which were highly correlated with a previous genome-wide CRISPR screen in K562 cells10 (r = 0.85)”
From Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens (2021) · cites this paper as [10]

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Authors: Wang, T., Birsoy, K., Hughes, N. W., Krupczak, K. M., Post, Y., Wei, J. J., Lander, E. S., & Sabatini, D. M.
Affiliations: Broad Institute (US)
Whitehead Institute for Biomedical Research (US)
Corresponding author: Lander, Eric S.
Sabatini, David M.
ORCID: Birsoy, Kıvanç
Hughes, Nicholas W.
Post, Yorick
Wei, Jenny J.
Lander, Eric S.
Sabatini, David M.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2015-11-27
Volume: 350
Issue: 6264
Pages: 1096-1101
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.aac7041
PMC: PMC4662922
OpenAlex: W1934704664
Cited by: 1,617
References: 51
Citations by year: 2026: 60 · 2025: 103 · 2024: 116 · 2023: 147 · 2022: 146 · 2021: 199 · 2020: 182 · 2019: 171 · 2018: 182 · 2017: 193 · 2016: 104 · 2015: 10 · 2014: 1 · 2013: 1
FWCI: 70.64
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.sciencemag.org/about/science-licenses-journal-article-reuse (vor, 366 d)
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Science Foundation
National Institutes of Health (CA103866)
Howard Hughes Medical Institute
National Human Genome Research Institute (2U54HG003067-10)
Massachussetts Institute of Technology Whitaker Health Sciences Fund
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords: essential genes, gene essentiality, CRISPR screen, single guide RNA library, cancer cell lines, RNA processing genes, nucleolus, cell proliferation and survival, cancer cell vulnerability, oncogenic drivers
MeSH terms: RNA, Guide, CRISPR-Cas Systems, Cell Nucleolus, Genetic Testing, Humans, Neoplasms, RNA Processing, Post-Transcriptional, Genomic Library, Genome, Human, Genes, Essential, Gene Expression Profiling, Cell Line, Tumor, Gene Knockout Techniques, CRISPR-Cas Systems

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Identification and characterization of essential genes in the human genome

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