Cited 22 times in
High-throughput functional evaluation of human cancer-associated mutations using base editors
DC Field | Value | Language |
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dc.contributor.author | 김영광 | - |
dc.contributor.author | 김형범 | - |
dc.contributor.author | 채동우 | - |
dc.contributor.author | 이승호 | - |
dc.date.accessioned | 2022-08-23T00:16:58Z | - |
dc.date.available | 2022-08-23T00:16:58Z | - |
dc.date.issued | 2022-06 | - |
dc.identifier.issn | 1087-0156 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/189350 | - |
dc.description.abstract | Comprehensive phenotypic characterization of the many mutations found in cancer tissues is one of the biggest challenges in cancer genomics. In this study, we evaluated the functional effects of 29,060 cancer-related transition mutations that result in protein variants on the survival and proliferation of non-tumorigenic lung cells using cytosine and adenine base editors and single guide RNA (sgRNA) libraries. By monitoring base editing efficiencies and outcomes using surrogate target sequences paired with sgRNA-encoding sequences on the lentiviral delivery construct, we identified sgRNAs that induced a single primary protein variant per sgRNA, enabling linking those mutations to the cellular phenotypes caused by base editing. The functions of the vast majority of the protein variants (28,458 variants, 98%) were classified as neutral or likely neutral; only 18 (0.06%) and 157 (0.5%) variants caused outgrowing and likely outgrowing phenotypes, respectively. We expect that our approach can be extended to more variants of unknown significance and other tumor types. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Nature America Publishing | - |
dc.relation.isPartOf | NATURE BIOTECHNOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | CRISPR-Cas Systems | - |
dc.subject.MESH | Gene Editing* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Mutation / genetics | - |
dc.subject.MESH | Neoplasms* / genetics | - |
dc.subject.MESH | RNA, Guide / genetics | - |
dc.title | High-throughput functional evaluation of human cancer-associated mutations using base editors | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pharmacology (약리학교실) | - |
dc.contributor.googleauthor | Younggwang Kim | - |
dc.contributor.googleauthor | Seungho Lee | - |
dc.contributor.googleauthor | Soohyuk Cho | - |
dc.contributor.googleauthor | Jinman Park | - |
dc.contributor.googleauthor | Dongwoo Chae | - |
dc.contributor.googleauthor | Taeyoung Park | - |
dc.contributor.googleauthor | John D Minna | - |
dc.contributor.googleauthor | Hyongbum Henry Kim | - |
dc.identifier.doi | 10.1038/s41587-022-01276-4 | - |
dc.contributor.localId | A05881 | - |
dc.contributor.localId | A01148 | - |
dc.contributor.localId | A04014 | - |
dc.relation.journalcode | J02290 | - |
dc.identifier.eissn | 1546-1696 | - |
dc.identifier.pmid | 35411116 | - |
dc.identifier.url | https://www.nature.com/articles/s41587-022-01276-4 | - |
dc.contributor.alternativeName | Kim, Younggwang | - |
dc.contributor.affiliatedAuthor | 김영광 | - |
dc.contributor.affiliatedAuthor | 김형범 | - |
dc.contributor.affiliatedAuthor | 채동우 | - |
dc.citation.volume | 40 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 874 | - |
dc.citation.endPage | 884 | - |
dc.identifier.bibliographicCitation | NATURE BIOTECHNOLOGY, Vol.40(6) : 874-884, 2022-06 | - |
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