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Identification and characterization of essential genes in the human genome
Open accessAbstract
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 1, 2 , drug resistance 3 , and viral infection 4 .”
From Pooled CRISPR screening with single-cell transcriptome readout. (2017) · cites this paper as [2]
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In the citing paper
“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
In the citing paper
“genome-scale application of CRISPR-Cas9 genome editing approaches offer the potential to map global genetic interaction networks in human cells (55–57)”
From A global genetic interaction network maps a wiring diagram of cellular function (2016) · cites this paper as [56]
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Metadata
- 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.
- Venue
- Science
- Published
- 2015-11-27
- Volume
- 350
- Issue
- 6264
- Pages
- 1096-1101
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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
- FWCI
- 70.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- 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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