The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Identifying chemogenetic interactions from CRISPR screens with drugZ
Open accessAbstract
BACKGROUND: Chemogenetic profiling enables the identification of gene mutations that enhance or suppress the activity of chemical compounds. This knowledge provides insights into drug mechanism of action, genetic vulnerabilities, and resistance mechanisms, all of which may help stratify patient populations and improve drug efficacy. CRISPR-based screening enables sensitive detection of drug-gene interactions directly in human cells, but until recently has primarily been used to screen only for resistance mechanisms. RESULTS: We present drugZ, an algorithm for identifying both synergistic and suppressor chemogenetic interactions from CRISPR screens. DrugZ identifies synthetic lethal interactions between PARP inhibitors and both known and novel members of the DNA damage repair pathway, confirms KEAP1 loss as a resistance factor for ERK inhibitors in oncogenic KRAS backgrounds, and defines the genetic context for temozolomide activity. CONCLUSIONS: DrugZ is an open-source Python software for the analysis of genome-scale drug modifier screens. The software accurately identifies genetic perturbations that enhance or suppress drug activity. Interestingly, analysis of new and previously published data reveals tumor suppressor genes are drug-agnostic resistance genes in drug modifier screens. The software is available at github.com/hart-lab/drugz .
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Lawson, K. A., Sousa, C. M., Zhang, X., Kim, E., Akthar, R., Caumanns, J. J., Yao, Y., Mikolajewicz, N., Ross, C., Brown, K. R., et al. (2020) · Nature · doi:10.1038/s41586-020-2746-2 · Cited by 443
Self-citationELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation
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Self-citationGenome-scale chemogenomic CRISPR screens in human cells using the TKOv3 library
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Metadata
- Authors
- Colic, M., Wang, G., Zimmermann, M., Mascall, K., McLaughlin, M., Bertolet, L., Lenoir, W. F., Moffat, J., Angers, S., Durocher, D., & Hart, T.
- Venue
- Genome Medicine
- Published
- 2019-08-22
- Volume
- 11
- Issue
- 1
- Pages
- 52-52
- ISSN
- 1756-994X (ISSN-L)
- OpenAlex
- W2969815104
- Cited by
- 219
- References
- 15
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- gold
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