A network of human functional gene interactions from knockout fitness screens in cancer cells.
Cell Line, Tumor
Clustered Regularly Interspaced Short Palindromic Repeats
/ genetics
Databases, Genetic
Gene Knockout Techniques
Gene Regulatory Networks
/ genetics
Genes, Neoplasm
/ genetics
Genotype
Humans
Neoplasms
/ genetics
Phenotype
Protein Biosynthesis
RNA, Small Interfering
/ genetics
Saccharomyces cerevisiae
/ genetics
Signal Transduction
/ genetics
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
12
12
2018
revised:
03
04
2019
accepted:
04
04
2019
entrez:
14
4
2019
pubmed:
14
4
2019
medline:
14
4
2019
Statut:
epublish
Résumé
Genetic interactions mediate the emergence of phenotype from genotype. The systematic survey of genetic interactions in yeast showed that genes operating in the same biological process have highly correlated genetic interaction profiles, and this observation has been exploited to infer gene function in model organisms. Such assays of digenic perturbations in human cells are also highly informative, but are not scalable, even with CRISPR-mediated methods. As an alternative, we developed an indirect method of deriving functional interactions. We show that genes having correlated knockout fitness profiles across diverse, non-isogenic cell lines are analogous to genes having correlated genetic interaction profiles across isogenic query strains and similarly imply shared biological function. We constructed a network of genes with correlated fitness profiles across 276 high-quality CRISPR knockout screens in cancer cell lines into a "coessentiality network," with up to 500-fold enrichment for co-functional gene pairs, enabling strong inference of gene function and highlighting the modular organization of the cell.
Identifiants
pubmed: 30979825
pii: 2/2/e201800278
doi: 10.26508/lsa.201800278
pmc: PMC6464042
pii:
doi:
Substances chimiques
RNA, Small Interfering
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM130119
Pays : United States
Informations de copyright
© 2019 Kim et al.
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