Population sequencing data reveal a compendium of mutational processes in the human germ line

doi:10.1126/science.aba7408

GSTDTAP > 气候变化

DOI	10.1126/science.aba7408
	Population sequencing data reveal a compendium of mutational processes in the human germ line
	Vladimir B. Seplyarskiy; Ruslan A. Soldatov; Evan Koch; Ryan J. McGinty; Jakob M. Goldmann; Ryan D. Hernandez; Kathleen Barnes; Adolfo Correa; Esteban G. Burchard; Patrick T. Ellinor; Stephen T. McGarvey; Braxton D. Mitchell; Ramachandran S. Vasan; Susan Redline; Edwin Silverman; Scott T. Weiss; Donna K. Arnett; John Blangero; Eric Boerwinkle; Jiang He; Courtney Montgomery; D. C. Rao; Jerome I. Rotter; Kent D. Taylor; Jennifer A. Brody; Yii-Der Ida Chen; Lisa de las Fuentes; Chii-Min Hwu; Stephen S. Rich; Ani W. Manichaikul; Josyf C. Mychaleckyj; Nicholette D. Palmer; Jennifer A. Smith; Sharon L. R. Kardia; Patricia A. Peyser; Lawrence F. Bielak; Timothy D. O’Connor; Leslie S. Emery; NHLBI Trans-Omics for Precision Medicine Consortium‡; TOPMed Population Genetics Working Group; Christian Gilissen; Wendy S. W. Wong; Peter V. Kharchenko; Shamil Sunyaev
	2021-08-27
发表期刊	Science
出版年	2021
英文摘要	It has become increasing clear that mutation affects phenotypic variation and disease risk across humans. However, there are many different types of mutation. Seplyarskiy et al. applied a matrix factorization method to large human genomic datasets to identify germline mutational processes in an unsupervised manner. From this survey, nine robust mutational components were identified and specific mechanisms generating seven of these processes were proposed from correlations with genomic features. These results confirm and improve upon our understanding of mutational processes and reveal likely mechanisms of mutation in the human genome. Science , aba7408, this issue p. [1030][1] Biological mechanisms underlying human germline mutations remain largely unknown. We statistically decompose variation in the rate and spectra of mutations along the genome using volume-regularized nonnegative matrix factorization. The analysis of a sequencing dataset (TOPMed) reveals nine processes that explain the variation in mutation properties between loci. We provide a biological interpretation for seven of these processes. We associate one process with bulky DNA lesions that are resolved asymmetrically with respect to transcription and replication. Two processes track direction of replication fork and replication timing, respectively. We identify a mutagenic effect of active demethylation primarily acting in regulatory regions and a mutagenic effect of long interspersed nuclear elements. We localize a mutagenic process specific to oocytes from population sequencing data. This process appears transcriptionally asymmetric. [1]: /lookup/doi/10.1126/science.aba7408
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/336671
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Vladimir B. Seplyarskiy,Ruslan A. Soldatov,Evan Koch,et al. Population sequencing data reveal a compendium of mutational processes in the human germ line[J]. Science,2021.
APA	Vladimir B. Seplyarskiy.,Ruslan A. Soldatov.,Evan Koch.,Ryan J. McGinty.,Jakob M. Goldmann.,...&Shamil Sunyaev.(2021).Population sequencing data reveal a compendium of mutational processes in the human germ line.Science.
MLA	Vladimir B. Seplyarskiy,et al."Population sequencing data reveal a compendium of mutational processes in the human germ line".Science (2021).