Review

. 2025 Jul;643(8070):47-59.

doi: 10.1038/s41586-025-09096-7. Epub 2025 Jul 2.

Collaborators, Affiliations

Collaborators

Somatic Mosaicism across Human Tissues Network:
Richard S Conroy, Brionna Y Hair, Walter J Koroshetz, Roger Little, Amy C Lossie, Jill A Morris, Dena C Procaccini, Wendy Wang, Casey Andrews, Sarah Cody, Milinn Kremitzki, Daofeng Li, Tina Lindsay, Wenjin Zhang, Valerie J Estela-Pro, Kayla Giancarlo, Melissa Grimm, Azra Hasan, M Kathryn Leonard, Phoebe McDermott, Mary Pfeiffer, Isabel Sleeman, Stephanie Bohaczuk, Colleen P Davis, Christian D Frazar, Kendra Hoekzema, Meng-Fan Huang, Caitlin Jacques, Dana M Jensen, J Thomas Kolar, Youngjun Kwon, Kelsey Loy, Yizi Mao, Min-Hwan Sohn, Katherine M Munson, Shane Neph, Jeffrey Ou, Nancy L Parmalee, Meranda M Pham, Jane Ranchalis, Luyao Ren, Adriana E Sedeño-Cortés, Joshua D Smith, Melanie Sorensen, Lila Sutherlin, Mitchell R Vollger, Chia-Lin Wei, Jeffrey M Weiss, Christina Zakarian, Natalie Y T Au, Amy Leonardson, Jiadong Lin, Taralynn Mack, Sean R McGee, Anna Minkina, Patrick M Nielsen, Chris Oliveira, Erica Ryke, Tristan Shaffer, Elliott G Swanson, Elizabeth G Atkinson, Sravya Bhamidipati, Hsu Chao, Christopher M Grochowski, Harsha V Doddapaneni, Divya Kalra, Ziad Khan, Kavya Kottapalli, Marie-Claude Gingras, Walker Hale, Heer Mehta, Donna M Muzny, Muchun Niu, Luis F Paulin, Jeffrey Rogers, Evette Scott, Fritz J Sedlazeck, Kimberly Walker, Tao Wu, Kristin G Ardlie, Viktor Adalsteinsson, Lisa Anderson, Carrie Cibulskis, Laura Domènech, Kiran Garimella, Whitney Hornsby, Steve Huang, Satoshi Koyama, Niall J Lennon, Tetsushi Nakao, Azeet Narayan, Evin Padhi, Constantijn Scharlee, Md Mesbah Uddin, Liying Xue, Zhi Yu, Shadi Zaheri, Ruolin Liu, Ning Stella Li, Hang Su, Derek Albracht, Eddie Belter, Emma Casey, Justin Chen, Yuchen Cheng, Shihua Dong, Qichen Fu, Robert Fulton, John Garza, H Josh Jang, Sheng Chih Jin, Benjamin K Johnson, Nahyun Kong, Daofeng Li, Zefan Li, Shane Liu, Juan F Macias-Velasco, Elvisa Mehinovic, Benpeng Miao, Theron Palmer, Purva Patel, Mary F Majewski, Daniel C Rohrer, Andrew Ruttenberg, Ayush Semwal, Jiawei Shen, Zitian Tang, Chad Tomlinson, Wenjin Zhang, Zilan Xin, Christina Missler, Brianne E Livermore, Jade E B Carter, William Driscoll, Uday S Evani, Heather Geiger, M Tausif Hasan, Manisha Kher, Rajeeva Musunuri, Giuseppe Narzisi, Nicolas Robine, Alexi Runnels, Mingyun Bae, Michele Berselli, Ann Caplin, Hye-Jung Elizabeth Chun, Niklas L Engel, William C Feng, Yan Gao, Dominik Glodzik, Yoo-Jin Jiny Ha, Hu Jin, Sehi L'Yi, Lovelace J Luquette, Maximilian Marin, Julia Markowski, Dominika Maziec, Huang Neng, Sarah Nicholson, Junseok Park, Qin Qian, Han Qu, Douglas Rioux, William Ronchetti, Andrew Schroeder, Corinne E Sexton, Yichen Si, Kar-Tong Tan, David Tang, Alexander D Veit, Vinayak V Viswanadham, Suenghyun Wang, Kyung Ah Woo, Xi Zeng, Yuwei Zhang, Yifan Zhao, Ying Zhou, Michail Andreopoulos, Shannon Ehmsen, Cesar Ferreyra-Mansilla, Clara TaeHee Kim, David Michaels, Bianca Morris, Brandt A Bessell, Ingrid Flashpohler, Steve Losh, Torrin L McDonald, Camille Mumm, Jessica A Switzenberg, Jinhao Wang, Weichen Zhou, Guanlan Dong, Nazia Hilal, Se-Young Jo, Shayna L Mallett, Monica Devi Manam, Shulin Mao, Christopher Walsh, Sijing Zhao, Yiling Elaine Huang, Abhiram Natu, Reenal Pattni, Carolin Purman, Bo Zhou, Xiaowei Zhu, Jiayi Luo, Yichi Niu, Rohan Thakur, David A Weitz, Yang Zhang, Yilei Fu, Michal B Izydorczyk, Luis F Paulin, Xiaomei Zhan, Xinchang Zheng, Geon Hue Bae, Taejeong Bae, Areum Cho, June Hyug Choi, Hyungbin Chun, Mrunal Dehankar, Yeongjun Jang, Seok-Won Jeong, Min Ji, Mee Sook Jun, Su Rim Kim, Seong Gyu Kwon, Soung-Hoon Lee, Nanda Maya Mali, Arijit Panda, Jung Min Park, JaeEun Shin, Milovan Suvakov, Gabor T Marth, Brad Demarest, Stephanie Gardiner, Stephanie J Georges, Yingqi Zhang, Sammantha Avaylon, Alexandre Pellan Cheng, Wei-Yu Chi, Mariela Cortés-López, Andrew R D'Avino, Husain Danish, Elliot Eton, Foteini Fotopoulo, Saravanan Ganesan, Yiyun Lin, Qing Luo, Levan Mekerishvili, Joe Pelt, Catherine Potenski, Tamara Prieto, Jake Qiu, Ivan Raimondi, Mandeep Singh, Dennis Yuan, John Zinno, Benjamin Costa, Jonathan Evan Shoag, Jimin Tan, Aristotelis Tsirigos, Nisrine T Jabara, Marta Grońska-Pęski, Emre Caglayan, Hayley Cline, Niklas L Engel, Shelbi E Gill, Robert Sean Hill, Andrea J Kriz, Julia Markowski, Alisa Mo, Daniel Snellings, Justin S Becker, Aidan H Burn, Wen-Chih Cheng, Jennifer A Karlow, Cheuk-Ting Law, Shayna L Mallet, Carlos Mendez-Dorantes, Khue H Nguyen, Adam Voshall, Boxun Zhao, Benno Orr, Andrew J C Russell, He Li, Yan Li, Leina Lu, Xiaofeng Zhu, Trishita Basak, Azita Ghodssi, Katrina Newcomer, Yuqing Wang

Affiliations

¹ Broad Institute of MIT and Harvard, Cambridge, MA, USA. tcoorens@broadinstitute.org.
² European Bioinformatics Institute, European Molecular Biology Laboratory (EMBL-EBI), Cambridge, UK. tcoorens@broadinstitute.org.
³ Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea. g1@yuhs.ac.
⁴ Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. g1@yuhs.ac.
⁵ Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
⁶ Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea.
⁷ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁸ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
⁹ Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
¹⁰ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹¹ Department of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
¹² McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
¹³ Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
¹⁴ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁵ New York Genome Center, New York, NY, USA.
¹⁶ National Disease Research Interchange, Philadelphia, PA, USA.
¹⁷ Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA.
¹⁸ Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA.
¹⁹ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
²⁰ Department of Pathology, Harvard Medical School, Boston, MA, USA.
²¹ Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
²² Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
²³ Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
²⁴ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
²⁵ Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
²⁶ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
²⁷ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
²⁸ Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
²⁹ Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
³⁰ Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, NY, USA.
³¹ Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA.
³² Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, NY, USA.
³³ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³⁴ Center for Behavioral Health, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, USA.
³⁵ Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
³⁶ Department of Genetics, Washington University, St. Louis, MO, USA.
³⁷ Program in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
³⁸ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
³⁹ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
⁴⁰ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴¹ Center for Pediatric Health Equity Research, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, USA.
⁴² Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
⁴³ Department of Computer and Data Sciences, School of Engineering, Case Western Reserve University, Cleveland, OH, USA.
⁴⁴ European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
⁴⁵ Bridging Research Division on Mechanisms of Genomic Variation and Data Science, German Cancer Research Center, Heidelberg, Germany.
⁴⁶ Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
⁴⁷ Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
⁴⁸ Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
⁴⁹ Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
⁵⁰ Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁵¹ Department of Human Genetics, University of Utah, Salt Lake City, UT, USA.
⁵² Lieber Institute for Brain Development, Baltimore, MD, USA.
⁵³ Department of Pathology, Stanford University, Stanford, CA, USA.
⁵⁴ Department of Genetics, Stanford University, Stanford, CA, USA.
⁵⁵ Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
⁵⁶ Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁵⁷ Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁵⁸ Ludwig Center at Harvard, Harvard Medical School, Boston, MA, USA.
⁵⁹ Center for Genomics and Systems Biology, New York University, New York, NY, USA.
⁶⁰ Department of Computer Science, Rice University, Houston, TX, USA.
⁶¹ Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
⁶² Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
⁶³ Brotman Baty Institute for Precision Medicine, Seattle, WA, USA.
⁶⁴ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
⁶⁵ Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
⁶⁶ Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
⁶⁷ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁶⁸ Howard Hughes Medical Institute, Boston, MA, USA.
⁶⁹ Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
⁷⁰ Roy M. and Phyllis Gough Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.
⁷¹ Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
⁷² Broad Institute of MIT and Harvard, Cambridge, MA, USA. ealice.lee@childrens.harvard.edu.
⁷³ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA. ealice.lee@childrens.harvard.edu.
⁷⁴ Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA. ealice.lee@childrens.harvard.edu.
⁷⁵ Department of Pediatrics, Harvard Medical School, Boston, MA, USA. ealice.lee@childrens.harvard.edu.
⁷⁶ Child Study Center, Yale University, New Haven, CT, USA. flora.vaccarino@yale.edu.
⁷⁷ Department of Neuroscience, Yale University, New Haven, CT, USA. flora.vaccarino@yale.edu.
⁷⁸ Yale Stem Cell Center, Yale University, New Haven, CT, USA. flora.vaccarino@yale.edu.

^# Contributed equally.

PMID: 40604182
DOI: 10.1038/s41586-025-09096-7

Review

The Somatic Mosaicism across Human Tissues Network

Tim H H Coorens et al. Nature. 2025 Jul.

. 2025 Jul;643(8070):47-59.

doi: 10.1038/s41586-025-09096-7. Epub 2025 Jul 2.

Authors

Collaborators

Somatic Mosaicism across Human Tissues Network:
Richard S Conroy, Brionna Y Hair, Walter J Koroshetz, Roger Little, Amy C Lossie, Jill A Morris, Dena C Procaccini, Wendy Wang, Casey Andrews, Sarah Cody, Milinn Kremitzki, Daofeng Li, Tina Lindsay, Wenjin Zhang, Valerie J Estela-Pro, Kayla Giancarlo, Melissa Grimm, Azra Hasan, M Kathryn Leonard, Phoebe McDermott, Mary Pfeiffer, Isabel Sleeman, Stephanie Bohaczuk, Colleen P Davis, Christian D Frazar, Kendra Hoekzema, Meng-Fan Huang, Caitlin Jacques, Dana M Jensen, J Thomas Kolar, Youngjun Kwon, Kelsey Loy, Yizi Mao, Min-Hwan Sohn, Katherine M Munson, Shane Neph, Jeffrey Ou, Nancy L Parmalee, Meranda M Pham, Jane Ranchalis, Luyao Ren, Adriana E Sedeño-Cortés, Joshua D Smith, Melanie Sorensen, Lila Sutherlin, Mitchell R Vollger, Chia-Lin Wei, Jeffrey M Weiss, Christina Zakarian, Natalie Y T Au, Amy Leonardson, Jiadong Lin, Taralynn Mack, Sean R McGee, Anna Minkina, Patrick M Nielsen, Chris Oliveira, Erica Ryke, Tristan Shaffer, Elliott G Swanson, Elizabeth G Atkinson, Sravya Bhamidipati, Hsu Chao, Christopher M Grochowski, Harsha V Doddapaneni, Divya Kalra, Ziad Khan, Kavya Kottapalli, Marie-Claude Gingras, Walker Hale, Heer Mehta, Donna M Muzny, Muchun Niu, Luis F Paulin, Jeffrey Rogers, Evette Scott, Fritz J Sedlazeck, Kimberly Walker, Tao Wu, Kristin G Ardlie, Viktor Adalsteinsson, Lisa Anderson, Carrie Cibulskis, Laura Domènech, Kiran Garimella, Whitney Hornsby, Steve Huang, Satoshi Koyama, Niall J Lennon, Tetsushi Nakao, Azeet Narayan, Evin Padhi, Constantijn Scharlee, Md Mesbah Uddin, Liying Xue, Zhi Yu, Shadi Zaheri, Ruolin Liu, Ning Stella Li, Hang Su, Derek Albracht, Eddie Belter, Emma Casey, Justin Chen, Yuchen Cheng, Shihua Dong, Qichen Fu, Robert Fulton, John Garza, H Josh Jang, Sheng Chih Jin, Benjamin K Johnson, Nahyun Kong, Daofeng Li, Zefan Li, Shane Liu, Juan F Macias-Velasco, Elvisa Mehinovic, Benpeng Miao, Theron Palmer, Purva Patel, Mary F Majewski, Daniel C Rohrer, Andrew Ruttenberg, Ayush Semwal, Jiawei Shen, Zitian Tang, Chad Tomlinson, Wenjin Zhang, Zilan Xin, Christina Missler, Brianne E Livermore, Jade E B Carter, William Driscoll, Uday S Evani, Heather Geiger, M Tausif Hasan, Manisha Kher, Rajeeva Musunuri, Giuseppe Narzisi, Nicolas Robine, Alexi Runnels, Mingyun Bae, Michele Berselli, Ann Caplin, Hye-Jung Elizabeth Chun, Niklas L Engel, William C Feng, Yan Gao, Dominik Glodzik, Yoo-Jin Jiny Ha, Hu Jin, Sehi L'Yi, Lovelace J Luquette, Maximilian Marin, Julia Markowski, Dominika Maziec, Huang Neng, Sarah Nicholson, Junseok Park, Qin Qian, Han Qu, Douglas Rioux, William Ronchetti, Andrew Schroeder, Corinne E Sexton, Yichen Si, Kar-Tong Tan, David Tang, Alexander D Veit, Vinayak V Viswanadham, Suenghyun Wang, Kyung Ah Woo, Xi Zeng, Yuwei Zhang, Yifan Zhao, Ying Zhou, Michail Andreopoulos, Shannon Ehmsen, Cesar Ferreyra-Mansilla, Clara TaeHee Kim, David Michaels, Bianca Morris, Brandt A Bessell, Ingrid Flashpohler, Steve Losh, Torrin L McDonald, Camille Mumm, Jessica A Switzenberg, Jinhao Wang, Weichen Zhou, Guanlan Dong, Nazia Hilal, Se-Young Jo, Shayna L Mallett, Monica Devi Manam, Shulin Mao, Christopher Walsh, Sijing Zhao, Yiling Elaine Huang, Abhiram Natu, Reenal Pattni, Carolin Purman, Bo Zhou, Xiaowei Zhu, Jiayi Luo, Yichi Niu, Rohan Thakur, David A Weitz, Yang Zhang, Yilei Fu, Michal B Izydorczyk, Luis F Paulin, Xiaomei Zhan, Xinchang Zheng, Geon Hue Bae, Taejeong Bae, Areum Cho, June Hyug Choi, Hyungbin Chun, Mrunal Dehankar, Yeongjun Jang, Seok-Won Jeong, Min Ji, Mee Sook Jun, Su Rim Kim, Seong Gyu Kwon, Soung-Hoon Lee, Nanda Maya Mali, Arijit Panda, Jung Min Park, JaeEun Shin, Milovan Suvakov, Gabor T Marth, Brad Demarest, Stephanie Gardiner, Stephanie J Georges, Yingqi Zhang, Sammantha Avaylon, Alexandre Pellan Cheng, Wei-Yu Chi, Mariela Cortés-López, Andrew R D'Avino, Husain Danish, Elliot Eton, Foteini Fotopoulo, Saravanan Ganesan, Yiyun Lin, Qing Luo, Levan Mekerishvili, Joe Pelt, Catherine Potenski, Tamara Prieto, Jake Qiu, Ivan Raimondi, Mandeep Singh, Dennis Yuan, John Zinno, Benjamin Costa, Jonathan Evan Shoag, Jimin Tan, Aristotelis Tsirigos, Nisrine T Jabara, Marta Grońska-Pęski, Emre Caglayan, Hayley Cline, Niklas L Engel, Shelbi E Gill, Robert Sean Hill, Andrea J Kriz, Julia Markowski, Alisa Mo, Daniel Snellings, Justin S Becker, Aidan H Burn, Wen-Chih Cheng, Jennifer A Karlow, Cheuk-Ting Law, Shayna L Mallet, Carlos Mendez-Dorantes, Khue H Nguyen, Adam Voshall, Boxun Zhao, Benno Orr, Andrew J C Russell, He Li, Yan Li, Leina Lu, Xiaofeng Zhu, Trishita Basak, Azita Ghodssi, Katrina Newcomer, Yuqing Wang

Affiliations

¹ Broad Institute of MIT and Harvard, Cambridge, MA, USA. tcoorens@broadinstitute.org.
² European Bioinformatics Institute, European Molecular Biology Laboratory (EMBL-EBI), Cambridge, UK. tcoorens@broadinstitute.org.
³ Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea. g1@yuhs.ac.
⁴ Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. g1@yuhs.ac.
⁵ Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
⁶ Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea.
⁷ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁸ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
⁹ Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
¹⁰ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹¹ Department of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
¹² McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
¹³ Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
¹⁴ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁵ New York Genome Center, New York, NY, USA.
¹⁶ National Disease Research Interchange, Philadelphia, PA, USA.
¹⁷ Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA.
¹⁸ Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA.
¹⁹ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
²⁰ Department of Pathology, Harvard Medical School, Boston, MA, USA.
²¹ Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
²² Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
²³ Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
²⁴ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
²⁵ Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
²⁶ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
²⁷ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
²⁸ Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
²⁹ Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
³⁰ Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, NY, USA.
³¹ Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA.
³² Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, NY, USA.
³³ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³⁴ Center for Behavioral Health, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, USA.
³⁵ Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
³⁶ Department of Genetics, Washington University, St. Louis, MO, USA.
³⁷ Program in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
³⁸ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
³⁹ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
⁴⁰ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴¹ Center for Pediatric Health Equity Research, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, USA.
⁴² Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
⁴³ Department of Computer and Data Sciences, School of Engineering, Case Western Reserve University, Cleveland, OH, USA.
⁴⁴ European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
⁴⁵ Bridging Research Division on Mechanisms of Genomic Variation and Data Science, German Cancer Research Center, Heidelberg, Germany.
⁴⁶ Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
⁴⁷ Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
⁴⁸ Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
⁴⁹ Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
⁵⁰ Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁵¹ Department of Human Genetics, University of Utah, Salt Lake City, UT, USA.
⁵² Lieber Institute for Brain Development, Baltimore, MD, USA.
⁵³ Department of Pathology, Stanford University, Stanford, CA, USA.
⁵⁴ Department of Genetics, Stanford University, Stanford, CA, USA.
⁵⁵ Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
⁵⁶ Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁵⁷ Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁵⁸ Ludwig Center at Harvard, Harvard Medical School, Boston, MA, USA.
⁵⁹ Center for Genomics and Systems Biology, New York University, New York, NY, USA.
⁶⁰ Department of Computer Science, Rice University, Houston, TX, USA.
⁶¹ Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
⁶² Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
⁶³ Brotman Baty Institute for Precision Medicine, Seattle, WA, USA.
⁶⁴ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
⁶⁵ Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
⁶⁶ Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
⁶⁷ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁶⁸ Howard Hughes Medical Institute, Boston, MA, USA.
⁶⁹ Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
⁷⁰ Roy M. and Phyllis Gough Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA.
⁷¹ Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
⁷² Broad Institute of MIT and Harvard, Cambridge, MA, USA. ealice.lee@childrens.harvard.edu.
⁷³ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA. ealice.lee@childrens.harvard.edu.
⁷⁴ Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA. ealice.lee@childrens.harvard.edu.
⁷⁵ Department of Pediatrics, Harvard Medical School, Boston, MA, USA. ealice.lee@childrens.harvard.edu.
⁷⁶ Child Study Center, Yale University, New Haven, CT, USA. flora.vaccarino@yale.edu.
⁷⁷ Department of Neuroscience, Yale University, New Haven, CT, USA. flora.vaccarino@yale.edu.
⁷⁸ Yale Stem Cell Center, Yale University, New Haven, CT, USA. flora.vaccarino@yale.edu.

^# Contributed equally.

PMID: 40604182
DOI: 10.1038/s41586-025-09096-7

Abstract

From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues Network, which aims to create a reference catalogue of somatic mutations and their clonal patterns across 19 different tissue sites from 150 non-diseased donors and develop new technologies and computational tools to detect somatic mutations and assess their phenotypic consequences, including clonal expansions. This strategy enables a comprehensive examination of the mutational landscape across the human body, and provides a comparison baseline for somatic mutation in diseases. This will lead to a deep understanding of somatic mutations and clonal expansions across the lifespan, as well as their roles in health, in ageing and, by comparison, in diseases.

PubMed Disclaimer

Conflict of interest statement

Competing interests: F.C. is an academic founder of Curio Biosciences and Doppler Biosciences, and scientific advisor for Amber Bio; F.C’s interests were reviewed and managed by the Broad Institute in accordance with their conflict-of-interest policies. G.G. receives research funds from IBM, Pharmacyclics/Abbvie, Bayer, Genentech, Calico, Ultima Genomics, Inocras, Google, Kite and Novartis; is an inventor on patent applications filed by the Broad Institute related to MSMuTect, MSMutSig, POLYSOLVER, SignatureAnalyzer-GPU, MSEye and MinimuMM-seq; is a founder, consultant and holds privately held equity in Scorpion Therapeutics and PreDICTA Biosciences; and was a consultant to Merck, all unrelated to the present work. E.E.E. is a scientific advisory board member of Variant Bio. C.Z. is a co-founder and equity holder of Pioneer Genomics and reports that Baylor College of Medicine filed a patent application related to the CompDuplex-seq or CompDup method. P.N. reports research grants from Allelica, Amgen, Apple, Boston Scientific, Cleerly, Genentech/Roche, Ionis, Novartis and Silence Therapeutics; personal fees from Allelica, Apple, AstraZeneca, Bain Capital, Blackstone Life Sciences, Bristol Myers Squibb, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Esperion Therapeutics, Foresite Capital, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, Merck, Novartis, Novo Nordisk, TenSixteen Bio and Tourmaline Bio; equity in Bolt, Candela, Mercury, MyOme, Parameter Health, Preciseli and TenSixteen Bio; and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. C.T. is the founder of C2T; a consultant for Bayer; a member of the scientific advisory board of PrognomiQ; and receives royalties from Exact Sciences. J.W.O. is the founder and CEO of Absolute DNA, with no direct relation to this study, and the interests are managed by University-Industry Foundation in Yonsei University Health System in accordance with their conflict-of-interest policies. E.A.L. is a member of the scientific advisory board for Inocras. All other authors declare no competing interests.

References

1. International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001). - DOI
1. Durbin, R. M. et al. A map of human genome variation from population-scale sequencing. Nature 467, 1061–1073 (2010). - PubMed - DOI
1. Wang, T. et al. The Human Pangenome Project: a global resource to map genomic diversity. Nature 604, 437–446 (2022). - PubMed - PMC - DOI
1. Stratton, M. R., Campbell, P. J. & Futreal, P. A. The cancer genome. Nature 458, 719–724 (2009). - PubMed - PMC - DOI
1. Saini, N. & Gordenin, D. A. Somatic mutation load and spectra: a record of DNA damage and repair in healthy human cells. Environ. Mol. Mutagen. 59, 672–686 (2018). - PubMed - PMC - DOI

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Nature Publishing Group

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The Somatic Mosaicism across Human Tissues Network

Collaborators

Affiliations

The Somatic Mosaicism across Human Tissues Network

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources