Please use this identifier to cite or link to this item:
https://doi.org/10.1186/s13059-021-02266-6
DC Field | Value | |
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dc.title | CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies | |
dc.contributor.author | Davies, Rebecca | |
dc.contributor.author | Liu, Ling | |
dc.contributor.author | Taotao, Sheng | |
dc.contributor.author | Tuano, Natasha | |
dc.contributor.author | Chaturvedi, Richa | |
dc.contributor.author | Huang, Kie Kyon | |
dc.contributor.author | Itman, Catherine | |
dc.contributor.author | Mandoli, Amit | |
dc.contributor.author | Qamra, Aditi | |
dc.contributor.author | Hu, Changyuan | |
dc.contributor.author | Powell, David | |
dc.contributor.author | Daly, Roger J. | |
dc.contributor.author | Tan, Patrick | |
dc.contributor.author | Rosenbluh, Joseph | |
dc.date.accessioned | 2022-10-13T01:09:50Z | |
dc.date.available | 2022-10-13T01:09:50Z | |
dc.date.issued | 2021-01-26 | |
dc.identifier.citation | Davies, Rebecca, Liu, Ling, Taotao, Sheng, Tuano, Natasha, Chaturvedi, Richa, Huang, Kie Kyon, Itman, Catherine, Mandoli, Amit, Qamra, Aditi, Hu, Changyuan, Powell, David, Daly, Roger J., Tan, Patrick, Rosenbluh, Joseph (2021-01-26). CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies. Genome Biology 22 (1) : 47. ScholarBank@NUS Repository. https://doi.org/10.1186/s13059-021-02266-6 | |
dc.identifier.issn | 1474-7596 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/232770 | |
dc.description.abstract | Introduction: Genes contain multiple promoters that can drive the expression of various transcript isoforms. Although transcript isoforms from the same gene could have diverse and non-overlapping functions, current loss-of-function methodologies are not able to differentiate between isoform-specific phenotypes. Results: Here, we show that CRISPR interference (CRISPRi) can be adopted for targeting specific promoters within a gene, enabling isoform-specific loss-of-function genetic screens. We use this strategy to test functional dependencies of 820 transcript isoforms that are gained in gastric cancer (GC). We identify a subset of GC-gained transcript isoform dependencies, and of these, we validate CIT kinase as a novel GC dependency. We further show that some genes express isoforms with opposite functions. Specifically, we find that the tumour suppressor ZFHX3 expresses an isoform that has a paradoxical oncogenic role that correlates with poor patient outcome. Conclusions: Our work finds isoform-specific phenotypes that would not be identified using current loss-of-function approaches that are not designed to target specific transcript isoforms. © 2021, The Author(s). | |
dc.publisher | BioMed Central Ltd | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Scopus OA2021 | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1186/s13059-021-02266-6 | |
dc.description.sourcetitle | Genome Biology | |
dc.description.volume | 22 | |
dc.description.issue | 1 | |
dc.description.page | 47 | |
Appears in Collections: | Elements Staff Publications |
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