مورد إلكتروني
Cancer-driving mutations are enriched in genic regions intolerant to germline variation
| العنوان: | Cancer-driving mutations are enriched in genic regions intolerant to germline variation |
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| المؤلفون: | Vitsios, D, Dhindsa, RS, Matelska, D, Mitchell, J, Zou, X, Armenia, J, Hu, F, Wang, Q, Sidders, B, Harper, AR, Petrovski, S |
| بيانات النشر: | AMER ASSOC ADVANCEMENT SCIENCE 2022-08-26 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Large reference datasets of protein-coding variation in human populations have allowed us to determine which genes and genic subregions are intolerant to germline genetic variation. There is also a growing number of genes implicated in severe Mendelian diseases that overlap with genes implicated in cancer. We hypothesized that cancer-driving mutations might be enriched in genic subregions that are depleted of germline variation relative to somatic variation. We introduce a new metric, OncMTR (oncology missense tolerance ratio), which uses 125,748 exomes in the Genome Aggregation Database (gnomAD) to identify these genic subregions. We demonstrate that OncMTR can significantly predict driver mutations implicated in hematologic malignancies. Divergent OncMTR regions were enriched for cancer-relevant protein domains, and overlaying OncMTR scores on protein structures identified functionally important protein residues. Last, we performed a rare variant, gene-based collapsing analysis on an independent set of 394,694 exomes from the UK Biobank and find that OncMTR markedly improves genetic signals for hematologic malignancies. |
| مصطلحات الفهرس: | Journal Article |
| URL: | |
| الإتاحة: | Open access content. Open access content CC BY-NC https://creativecommons.org/licenses/by-nc/4.0 |
| أرقام أخرى: | UMV oai:jupiter.its.unimelb.edu.au:11343/335821 Vitsios, D., Dhindsa, R. S., Matelska, D., Mitchell, J., Zou, X., Armenia, J., Hu, F., Wang, Q., Sidders, B., Harper, A. R. & Petrovski, S. (2022). Cancer-driving mutations are enriched in genic regions intolerant to germline variation. SCIENCE ADVANCES, 8 (34), https://doi.org/10.1126/sciadv.abo6371. 10.1126/sciadv.abo6371 2375-2548 2375-2548 1397544762 |
| المصدر المساهم: | UNIV OF MELBOURNE From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1397544762 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |