Comprehensive identification of somatic nucleotide variants in human brain tissue

Wang, Yifan; Bae, Taejeong; Thorpe, Jeremy; Sherman, Maxwell A.; Jones, Attila G.; Cho, Sean; Daily, Kenneth; Dou, Yanmei; Ganz, Javier; Galor, Alon; Lobon, Irene; Pattni, Reenal; Rosenbluh, Chaggai; Tomasi, Simone; Tomasini, Livia; Yang, Xiaoxu; Zhou, Bo; Akbarian, Schahram; Ball, Laurel L.; Bizzotto, Sara; Emery, Sarah B.; Doan, Ryan; Fasching, Liana; Jang, Yeongjun; Juan, David; Lizano, Esther; Luquette, Lovelace J.; Moldovan, John B.; Narurkar, Rujuta; Oetjens, Matthew T.; Rodin, Rachel E.; Sekar, Shobana.; Shin, Joo Heon; Soriano García, Eduardo; Straub, Richard E.; Zhou, Weichen; Chess, Andrew; Gleeson, Joseph G.; Marquès i Bonet, Tomàs, 1975-; Park, Peter J.; Peters, Mette A.; Pevsner, Jonathan; Walsh, Christopher A.; Weinberger, Daniel R.; Brain Somatic Mosaicism Network; Moran, John V.; Urban, Alexander E.; Kidd, Jeffrey M.; Mills, Ryan E.; Abyzov, Alexej

Comprehensive identification of somatic nucleotide variants in human brain tissue

Background: Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses...

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Autores:	Wang, Yifan, Bae, Taejeong, Thorpe, Jeremy, Sherman, Maxwell A., Jones, Attila G., Cho, Sean, Daily, Kenneth, Dou, Yanmei, Ganz, Javier, Galor, Alon, Lobon, Irene, Pattni, Reenal, Rosenbluh, Chaggai, Tomasi, Simone, Tomasini, Livia, Yang, Xiaoxu, Zhou, Bo, Akbarian, Schahram, Ball, Laurel L., Bizzotto, Sara, Emery, Sarah B., Doan, Ryan, Fasching, Liana, Jang, Yeongjun, Juan, David, Lizano, Esther, Luquette, Lovelace J., Moldovan, John B., Narurkar, Rujuta, Oetjens, Matthew T., Rodin, Rachel E., Sekar, Shobana., Shin, Joo Heon, Soriano García, Eduardo, Straub, Richard E., Zhou, Weichen, Chess, Andrew, Gleeson, Joseph G., Marquès i Bonet, Tomàs, 1975-, Park, Peter J., Peters, Mette A., Pevsner, Jonathan, Walsh, Christopher A., Weinberger, Daniel R., Brain Somatic Mosaicism Network, Moran, John V., Urban, Alexander E., Kidd, Jeffrey M., Mills, Ryan E., Abyzov, Alexej
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2021
País:	España
Institución:	Universidad de Barcelona
Repositorio:	Dipòsit Digital de la UB
OAI Identifier:	oai:diposit.ub.edu:2445/185960
Acceso en línea:	https://hdl.handle.net/2445/185960
Access Level:	acceso abierto
Palabra clave:	Malalties Neuropsiquiatria Reparació de l'ADN Duplicació de l'ADN Diseases Neuropsychiatry DNA repair DNA replication

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spelling	Comprehensive identification of somatic nucleotide variants in human brain tissueWang, YifanBae, TaejeongThorpe, JeremySherman, Maxwell A.Jones, Attila G.Cho, SeanDaily, KennethDou, YanmeiGanz, JavierGalor, AlonLobon, IrenePattni, ReenalRosenbluh, ChaggaiTomasi, SimoneTomasini, LiviaYang, XiaoxuZhou, BoAkbarian, SchahramBall, Laurel L.Bizzotto, SaraEmery, Sarah B.Doan, RyanFasching, LianaJang, YeongjunJuan, DavidLizano, EstherLuquette, Lovelace J.Moldovan, John B.Narurkar, RujutaOetjens, Matthew T.Rodin, Rachel E.Sekar, Shobana.Shin, Joo HeonSoriano García, EduardoStraub, Richard E.Zhou, WeichenChess, AndrewGleeson, Joseph G.Marquès i Bonet, Tomàs, 1975-Park, Peter J.Peters, Mette A.Pevsner, JonathanWalsh, Christopher A.Weinberger, Daniel R.Brain Somatic Mosaicism NetworkMoran, John V.Urban, Alexander E.Kidd, Jeffrey M.Mills, Ryan E.Abyzov, AlexejMalaltiesNeuropsiquiatriaReparació de l'ADNDuplicació de l'ADNDiseasesNeuropsychiatryDNA repairDNA replicationBackground: Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses significant challenges, particularly if the variants only are present in a small fraction of cells. Results: Here, the Brain Somatic Mosaicism Network conducts a coordinated, multi-institutional study to examine the ability of existing methods to detect simulated somatic single-nucleotide variants (SNVs) in DNA mixing experiments, generate multiple replicates of whole-genome sequencing data from the dorsolateral prefrontal cortex, other brain regions, dura mater, and dural fibroblasts of a single neurotypical individual, devise strategies to discover somatic SNVs, and apply various approaches to validate somatic SNVs. These efforts lead to the identification of 43 bona fide somatic SNVs that range in variant allele fractions from ~ 0.005 to ~ 0.28. Guided by these results, we devise best practices for calling mosaic SNVs from 250× whole-genome sequencing data in the accessible portion of the human genome that achieve 90% specificity and sensitivity. Finally, we demonstrate that analysis of multiple bulk DNA samples from a single individual allows the reconstruction of early developmental cell lineage trees. Conclusions: This study provides a unified set of best practices to detect somatic SNVs in non-cancerous tissues. The data and methods are freely available to the scientific community and should serve as a guide to assess the contributions of somatic SNVs to neuropsychiatric diseases.BioMed Central2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/185960Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s13059-021-02285-3Genome Biology, 2021, vol. 22, num. 92, p. 1-32https://doi.org/10.1186/s13059-021-02285-3cc-by (c) Wang, Yifan et al., 2021https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1859602026-05-27T06:46:51Z
dc.title.none.fl_str_mv	Comprehensive identification of somatic nucleotide variants in human brain tissue
title	Comprehensive identification of somatic nucleotide variants in human brain tissue
spellingShingle	Comprehensive identification of somatic nucleotide variants in human brain tissue Wang, Yifan Malalties Neuropsiquiatria Reparació de l'ADN Duplicació de l'ADN Diseases Neuropsychiatry DNA repair DNA replication
title_short	Comprehensive identification of somatic nucleotide variants in human brain tissue
title_full	Comprehensive identification of somatic nucleotide variants in human brain tissue
title_fullStr	Comprehensive identification of somatic nucleotide variants in human brain tissue
title_full_unstemmed	Comprehensive identification of somatic nucleotide variants in human brain tissue
title_sort	Comprehensive identification of somatic nucleotide variants in human brain tissue
dc.creator.none.fl_str_mv	Wang, Yifan Bae, Taejeong Thorpe, Jeremy Sherman, Maxwell A. Jones, Attila G. Cho, Sean Daily, Kenneth Dou, Yanmei Ganz, Javier Galor, Alon Lobon, Irene Pattni, Reenal Rosenbluh, Chaggai Tomasi, Simone Tomasini, Livia Yang, Xiaoxu Zhou, Bo Akbarian, Schahram Ball, Laurel L. Bizzotto, Sara Emery, Sarah B. Doan, Ryan Fasching, Liana Jang, Yeongjun Juan, David Lizano, Esther Luquette, Lovelace J. Moldovan, John B. Narurkar, Rujuta Oetjens, Matthew T. Rodin, Rachel E. Sekar, Shobana. Shin, Joo Heon Soriano García, Eduardo Straub, Richard E. Zhou, Weichen Chess, Andrew Gleeson, Joseph G. Marquès i Bonet, Tomàs, 1975- Park, Peter J. Peters, Mette A. Pevsner, Jonathan Walsh, Christopher A. Weinberger, Daniel R. Brain Somatic Mosaicism Network Moran, John V. Urban, Alexander E. Kidd, Jeffrey M. Mills, Ryan E. Abyzov, Alexej
author	Wang, Yifan
author_facet	Wang, Yifan Bae, Taejeong Thorpe, Jeremy Sherman, Maxwell A. Jones, Attila G. Cho, Sean Daily, Kenneth Dou, Yanmei Ganz, Javier Galor, Alon Lobon, Irene Pattni, Reenal Rosenbluh, Chaggai Tomasi, Simone Tomasini, Livia Yang, Xiaoxu Zhou, Bo Akbarian, Schahram Ball, Laurel L. Bizzotto, Sara Emery, Sarah B. Doan, Ryan Fasching, Liana Jang, Yeongjun Juan, David Lizano, Esther Luquette, Lovelace J. Moldovan, John B. Narurkar, Rujuta Oetjens, Matthew T. Rodin, Rachel E. Sekar, Shobana. Shin, Joo Heon Soriano García, Eduardo Straub, Richard E. Zhou, Weichen Chess, Andrew Gleeson, Joseph G. Marquès i Bonet, Tomàs, 1975- Park, Peter J. Peters, Mette A. Pevsner, Jonathan Walsh, Christopher A. Weinberger, Daniel R. Brain Somatic Mosaicism Network Moran, John V. Urban, Alexander E. Kidd, Jeffrey M. Mills, Ryan E. Abyzov, Alexej
author_role	author
author2	Bae, Taejeong Thorpe, Jeremy Sherman, Maxwell A. Jones, Attila G. Cho, Sean Daily, Kenneth Dou, Yanmei Ganz, Javier Galor, Alon Lobon, Irene Pattni, Reenal Rosenbluh, Chaggai Tomasi, Simone Tomasini, Livia Yang, Xiaoxu Zhou, Bo Akbarian, Schahram Ball, Laurel L. Bizzotto, Sara Emery, Sarah B. Doan, Ryan Fasching, Liana Jang, Yeongjun Juan, David Lizano, Esther Luquette, Lovelace J. Moldovan, John B. Narurkar, Rujuta Oetjens, Matthew T. Rodin, Rachel E. Sekar, Shobana. Shin, Joo Heon Soriano García, Eduardo Straub, Richard E. Zhou, Weichen Chess, Andrew Gleeson, Joseph G. Marquès i Bonet, Tomàs, 1975- Park, Peter J. Peters, Mette A. Pevsner, Jonathan Walsh, Christopher A. Weinberger, Daniel R. Brain Somatic Mosaicism Network Moran, John V. Urban, Alexander E. Kidd, Jeffrey M. Mills, Ryan E. Abyzov, Alexej
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Malalties Neuropsiquiatria Reparació de l'ADN Duplicació de l'ADN Diseases Neuropsychiatry DNA repair DNA replication
topic	Malalties Neuropsiquiatria Reparació de l'ADN Duplicació de l'ADN Diseases Neuropsychiatry DNA repair DNA replication
description	Background: Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses significant challenges, particularly if the variants only are present in a small fraction of cells. Results: Here, the Brain Somatic Mosaicism Network conducts a coordinated, multi-institutional study to examine the ability of existing methods to detect simulated somatic single-nucleotide variants (SNVs) in DNA mixing experiments, generate multiple replicates of whole-genome sequencing data from the dorsolateral prefrontal cortex, other brain regions, dura mater, and dural fibroblasts of a single neurotypical individual, devise strategies to discover somatic SNVs, and apply various approaches to validate somatic SNVs. These efforts lead to the identification of 43 bona fide somatic SNVs that range in variant allele fractions from ~ 0.005 to ~ 0.28. Guided by these results, we devise best practices for calling mosaic SNVs from 250× whole-genome sequencing data in the accessible portion of the human genome that achieve 90% specificity and sensitivity. Finally, we demonstrate that analysis of multiple bulk DNA samples from a single individual allows the reconstruction of early developmental cell lineage trees. Conclusions: This study provides a unified set of best practices to detect somatic SNVs in non-cancerous tissues. The data and methods are freely available to the scientific community and should serve as a guide to assess the contributions of somatic SNVs to neuropsychiatric diseases.
publishDate	2021
dc.date.none.fl_str_mv	2021
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/185960
url	https://hdl.handle.net/2445/185960
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1186/s13059-021-02285-3 Genome Biology, 2021, vol. 22, num. 92, p. 1-32 https://doi.org/10.1186/s13059-021-02285-3
dc.rights.none.fl_str_mv	cc-by (c) Wang, Yifan et al., 2021 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by (c) Wang, Yifan et al., 2021 https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	BioMed Central
publisher.none.fl_str_mv	BioMed Central
dc.source.none.fl_str_mv	Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona
instname_str	Universidad de Barcelona
reponame_str	Dipòsit Digital de la UB
collection	Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Comprehensive identification of somatic nucleotide variants in human brain tissue

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