Comprehensive identification of somatic nucleotide variants in human brain tissue
Wang, Yifan (University of Michigan Medical School. Department of Computational Medicine and Bioinformatics)
Bae, Taejeong (Mayo Clinic. Center for Individualized Medicine. Department of Health Sciences Research)
Thorpe, Jeremy (Johns Hopkins School of Medicine. Program in Biochemistry, Cellular and Molecular Biology)
Sherman, Maxwell A. (Harvard Medical School)
Jones, Attila G. (Icahn School of Medicine at Mount Sinai. Department of Genetics and Genomic Sciences)
Cho, Sean (Kennedy Krieger Institute. Department of Neurology)
Daily, Kenneth (Sage Bionetworks (Seattle, Estats Units))
Dou, Yanmei (Harvard Medical School. Department of Biomedical Informatics)
Ganz, Javier (Harvard Medical School. Departments of Neurology and Pediatrics)
Galor, Alon (Harvard Medical School. Department of Biomedical Informatics)
Lobón, Irene (Universitat de Barcelona. Departament de Biologia Cel·lular, Fisiologia i Immunologia)
Pattni, Reenal (Stanford University School of Medicine. Department of Genetics)
Rosenbluh, Chaggai (Icahn School of Medicine at Mount Sinai. Department of Cell, Developmental and Regenerative Biology)
Tomasi, Simone (Yale University. Child Study Center)
Tomasini, Livia (Yale University. Child Study Center)
Yang, Xiaoxu (Rady Children's Institute for Genomic Medicine)
Zhou, Bo (Stanford University School of Medicine. Department of Genetics)
Akbarian, Schahram (Icahn School of Medicine at Mount Sinai. Department of Psychiatry)
Ball, Laurel L. (Rady Children's Institute for Genomic Medicine)
Bizzotto, Sara (Broad Institute of MIT and Harvard)
Emery, Sarah B. (University of Michigan Medical School. Department of Human Genetics)
Doan, Ryan (Broad Institute of MIT and Harvard)
Fasching, Liana (Yale University. Child Study Center)
Jang, Yeongjun (Mayo Clinic. Center for Individualized Medicine. Department of Health Sciences Research)
Juan, David (Institut de Biologia Evolutiva (UPF-CSIC) (Barcelona))
Lizano, Esther (Institut de Biologia Evolutiva (UPF-CSIC) (Barcelona))
Luquette, Lovelace J. (Harvard Medical School. Department of Biomedical Informatics)
Moldovan, John B. (University of Michigan Medical School. Department of Human Genetics)
Narurkar, Rujuta (Lieber Institute for Brain Development)
Oetjens, Matthew T. (University of Michigan Medical School. Department of Human Genetics)
Rodin, Rachel E. (Broad Institute of MIT and Harvard)
Sekar, Shobana (Mayo Clinic. Center for Individualized Medicine. Department of Health Sciences Research)
Shin, Joo Heon (Johns Hopkins School of Medicine. Department of Neurology)
Soriano García, Eduardo (Universitat de Barcelona. Departament de Biologia Cel·lular, Fisiologia i Immunologia)
Straub, Richard E. (Lieber Institute for Brain Development)
Zhou, Weichen (University of Michigan Medical School. Department of Computational Medicine and Bioinformatics)
Chess, Andrew (Icahn School of Medicine at Mount Sinai. Department of Genetics and Genomic Sciences)
Gleeson, Joseph G. (Rady Children's Institute for Genomic Medicine)
Marques-Bonet, Tomas 1975- (Institut Català de Paleontologia Miquel Crusafont)
Park, Peter J. (Harvard Medical School. Department of Biomedical Informatics)
Peters, Mette A. (Sage Bionetworks)
Pevsner, Jonathan (Johns Hopkins School of Medicine. Department of Psychiatry and Behavioral Sciences)
Walsh, Christopher A. (Broad Institute of MIT and Harvard)
Weinberger, Daniel R. (Johns Hopkins School of Medicine. Department of Neuroscience)
Vaccarino, Flora M. (Yale University. Department of Neuroscience)
Moran, John V. (University of Michigan Medical School. Department of Internal Medicine)
Urban, Alexander E. (Stanford University School of Medicine. Department of Psychiatry and Behavioral Sciences)
Kidd, Jeffrey M. (University of Michigan Medical School. Department of Computational Medicine and Bioinformatics)
Mills, Ryan E. (University of Michigan Medical School. Department of Computational Medicine and Bioinformatics)
Abyzov, Alexej (Mayo Clinic. Center for Individualized Medicine. Department of Health Sciences Research)
Brain Somatic Mosaicism Network

Date:	2021
Abstract:	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. 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. 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. The online version contains supplementary material available at 10. 1186/s13059-021-02285-3.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Genome biology, Vol. 22 (march 2021) , ISSN 1474-760X

DOI: 10.1186/s13059-021-02285-3
PMID: 33781308

32 p, 2.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > Institut Català de Paleontologia Miquel Crusafont (ICP)
Articles > Research articles
Articles > Published articles