uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities
Donnelly Ctr, Toronto, ON M5S 3E1, Canada..
Donnelly Ctr, Toronto, ON M5S 3E1, Canada.;Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada..
Donnelly Ctr, Toronto, ON M5S 3E1, Canada..
Univ Toronto, Dept Pharmaceut Sci, Toronto, ON M5S 1A1, Canada.;Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 1A1, Canada..
Show others and affiliations
2015 (English)In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 163, no 6Article in journal (Refereed) Published
Resource type
Text
Abstract [en]

The ability to perturb genes in human cells is crucial for elucidating gene function and holds great potential for finding therapeutic targets for diseases such as cancer. To extend the catalog of human core and context-dependent fitness genes, we have developed a high-complexity second-generation genome-scale CRISPR-Cas9 gRNA library and applied it to fitness screens in five human cell lines. Using an improved Bayesian analytical approach, we consistently discover 5-fold more fitness genes than were previously observed. We present a list of 1,580 human core fitness genes and describe their general properties. Moreover, we demonstrate that context-dependent fitness genes accurately recapitulate pathway-specific genetic vulnerabilities induced by known oncogenes and reveal cell-type-specific dependencies for specific receptor tyrosine kinases, even in oncogenic KRAS backgrounds. Thus, rigorous identification of human cell line fitness genes using a high-complexity CRISPR-Cas9 library affords a high-resolution view of the genetic vulnerabilities of a cell.

Place, publisher, year, edition, pages
2015. Vol. 163, no 6
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-272070DOI: 10.1016/j.cell.2015.11.015ISI: 000366044800004PubMedID: 26627737OAI: oai:DiVA.org:uu-272070DiVA: diva2:892890
Funder
Swedish Research Council
Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2017-12-01Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Sun, Song

Search in DiVA

By author/editor
Sun, Song
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
Cell
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 594 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf