期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31878-0
关键词
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资金
- European Research Council [682398]
- ERDF/Spanish Ministry of Science, Innovation and Universities - Spanish State Research Agency/DamReMap Project [RTI2018-094095-B-I00]
- Asociacion Espanola Contra el Cancer (AECC) [GC16173697BIGA]
- Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO
- Government of Spain)
- CERCA (Generalitat de Catalunya)
- BIST PhD fellowship - Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia
- Barcelona Institute of Science and Technology (BIST)
- European Research Council (ERC) [682398] Funding Source: European Research Council (ERC)
Positive selection signals can be used to identify genes that drive clonal hematopoiesis in hematopoietic stem cells. By analyzing samples from two large cancer genomics cohorts, we obtained a list of nearly 70 candidate genes with positive selection signals. This approach can discover new CH genes and validate known CH genes.
Mutations in genes that confer a selective advantage to hematopoietic stem cells (HSCs) drive clonal hematopoiesis (CH). While some CH drivers have been identified, the compendium of all genes able to drive CH upon mutations in HSCs remains incomplete. Exploiting signals of positive selection in blood somatic mutations may be an effective way to identify CH driver genes, analogously to cancer. Using the tumor sample in blood/tumor pairs as reference, we identify blood somatic mutations across more than 12,000 donors from two large cancer genomics cohorts. The application of IntOGen, a driver discovery pipeline, to both cohorts, and more than 24,000 targeted sequenced samples yields a list of close to 70 genes with signals of positive selection in CH, available at . This approach recovers known CH genes, and discovers other candidates.
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