Title |
High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities
|
---|---|
Published in |
Cell, November 2015
|
DOI | 10.1016/j.cell.2015.11.015 |
Pubmed ID | |
Authors |
Traver Hart, Megha Chandrashekhar, Michael Aregger, Zachary Steinhart, Kevin R. Brown, Graham MacLeod, Monika Mis, Michal Zimmermann, Amelie Fradet-Turcotte, Song Sun, Patricia Mero, Peter Dirks, Sachdev Sidhu, Frederick P. Roth, Olivia S. Rissland, Daniel Durocher, Stephane Angers, Jason Moffat |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 22 | 30% |
Canada | 7 | 9% |
Spain | 5 | 7% |
United Kingdom | 2 | 3% |
Italy | 2 | 3% |
Japan | 2 | 3% |
Germany | 2 | 3% |
France | 1 | 1% |
Australia | 1 | 1% |
Other | 6 | 8% |
Unknown | 24 | 32% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 45 | 61% |
Scientists | 27 | 36% |
Science communicators (journalists, bloggers, editors) | 1 | 1% |
Practitioners (doctors, other healthcare professionals) | 1 | 1% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 9 | <1% |
United Kingdom | 7 | <1% |
Germany | 6 | <1% |
Canada | 5 | <1% |
Sweden | 3 | <1% |
Finland | 2 | <1% |
France | 1 | <1% |
India | 1 | <1% |
Austria | 1 | <1% |
Other | 7 | <1% |
Unknown | 1974 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 488 | 24% |
Researcher | 425 | 21% |
Student > Bachelor | 193 | 10% |
Student > Master | 178 | 9% |
Student > Doctoral Student | 80 | 4% |
Other | 269 | 13% |
Unknown | 383 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 754 | 37% |
Agricultural and Biological Sciences | 503 | 25% |
Medicine and Dentistry | 117 | 6% |
Immunology and Microbiology | 42 | 2% |
Computer Science | 36 | 2% |
Other | 151 | 7% |
Unknown | 413 | 20% |