%0 Journal Article %1 seplyarskiy2021population %A Seplyarskiy, Vladimir B. %A Soldatov, Ruslan A. %A Koch, Evan %A McGinty, Ryan J. %A Goldmann, Jakob M. %A Hernandez, Ryan D. %A Barnes, Kathleen %A Correa, Adolfo %A Burchard, Esteban G. %A Ellinor, Patrick T. %A McGarvey, Stephen T. %A Mitchell, Braxton D. %A Vasan, Ramachandran S. %A Redline, Susan %A Silverman, Edwin %A Weiss, Scott T. %A Arnett, Donna K. %A Blangero, John %A Boerwinkle, Eric %A He, Jiang %A Montgomery, Courtney %A Rao, D.C. %A Rotter, Jerome I. %A Taylor, Kent D. %A Brody, Jennifer A %A Chen, Yii-Der Ida %A de las Fuentes, Lisa %A Hwu, Chii-Min %A Rich, Stephen S. %A Manichaikul, Ani W. %A Mychaleckyj, Josyf C. %A Palmer, Nicholette D. %A Smith, Jennifer A. %A Kardia, Sharon L.R. %A Peyser, Patricia A. %A Bielak, Lawrence F. %A O’Connor, Timothy D. %A Emery, Leslie S. %A for Precision Medicine (TOPMed) Consortium, NHLBI Trans-Omics %A Group, TOPMed Population Genetics Working %A Gilissen, Christian %A Wong, Wendy S. W. %A Kharchenko, Peter V. %A Sunyaev, Shamil %D 2021 %I American Association for the Advancement of Science %J Science %K mutation_spectrum %R 10.1126/science.aba7408 %T Population sequencing data reveal a compendium of mutational processes in the human germ line %U https://science.sciencemag.org/content/early/2021/08/11/science.aba7408 %X 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 resolve 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 LINE repeats. We localize a mutagenic process specific to oocytes from population sequencing data. This process appears transcriptionally asymmetric.

@article{seplyarskiy2021population, abstract = {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 resolve 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 LINE repeats. We localize a mutagenic process specific to oocytes from population sequencing data. This process appears transcriptionally asymmetric.}, added-at = {2021-08-13T18:13:59.000+0200}, author = {Seplyarskiy, Vladimir B. and Soldatov, Ruslan A. and Koch, Evan and McGinty, Ryan J. and Goldmann, Jakob M. and Hernandez, Ryan D. and Barnes, Kathleen and Correa, Adolfo and Burchard, Esteban G. and Ellinor, Patrick T. and McGarvey, Stephen T. and Mitchell, Braxton D. and Vasan, Ramachandran S. and Redline, Susan and Silverman, Edwin and Weiss, Scott T. and Arnett, Donna K. and Blangero, John and Boerwinkle, Eric and He, Jiang and Montgomery, Courtney and Rao, D.C. and Rotter, Jerome I. and Taylor, Kent D. and Brody, Jennifer A and Chen, Yii-Der Ida and de las Fuentes, Lisa and Hwu, Chii-Min and Rich, Stephen S. and Manichaikul, Ani W. and Mychaleckyj, Josyf C. and Palmer, Nicholette D. and Smith, Jennifer A. and Kardia, Sharon L.R. and Peyser, Patricia A. and Bielak, Lawrence F. and O{\textquoteright}Connor, Timothy D. and Emery, Leslie S. and for Precision Medicine (TOPMed) Consortium, NHLBI Trans-Omics and Group, TOPMed Population Genetics Working and Gilissen, Christian and Wong, Wendy S. W. and Kharchenko, Peter V. and Sunyaev, Shamil}, biburl = {https://www.bibsonomy.org/bibtex/2fd19d19ffd4d48c2f3ef65a64551e9e5/peter.ralph}, doi = {10.1126/science.aba7408}, elocation-id = {eaba7408}, eprint = {https://science.sciencemag.org/content/early/2021/08/11/science.aba7408.full.pdf}, interhash = {b5c21be0bf00f30d9bf4c272f89e02d3}, intrahash = {fd19d19ffd4d48c2f3ef65a64551e9e5}, issn = {0036-8075}, journal = {Science}, keywords = {mutation_spectrum}, publisher = {American Association for the Advancement of Science}, timestamp = {2021-08-13T18:13:59.000+0200}, title = {Population sequencing data reveal a compendium of mutational processes in the human germ line}, url = {https://science.sciencemag.org/content/early/2021/08/11/science.aba7408}, year = 2021 }