Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements

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Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements
 
Luquette, Lovelace J.; Miller, Michael B.; Zhou, Zinan; Bohrson, Craig L.; Zhao, Yifan; Jin, Hu; Gulhan, Doga; Ganz, Javier; Bizzotto, Sara; Kirkham, Samantha; Hochepied, Tino; Libert, Claude; Galor, Alon; Kim, Junho; Lodato, Michael A.; Garaycoechea, Juan I.; Gawad, Charles; West, Jay; Walsh, Christopher A.; Park, Peter J.
(2022) Nature Genetics, volume 54, issue 10, pp. 1564 - 1571
(Article)
Abstract
Accurate somatic mutation detection from single-cell DNA sequencing is challenging due to amplification-related artifacts. To reduce this artifact burden, an improved amplification technique, primary template-directed amplification (PTA), was recently introduced. We analyzed whole-genome sequencing data from 52 PTA-amplified single neurons using SCAN2, a new genotyper we developed to leverage mutation ... read more
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Keywords: Genetics
DOI: https://doi.org/10.1038/s41588-022-01180-2
ISSN: 1061-4036
Publisher: Nature Publishing Group
Note: Funding Information: We thank R. S. Hill, R. Mathieu and L. (Sahithi) Cheemalamarri at the Boston Children’s Hospital & Harvard Stem Cell Institute Flow Cytometry Research Facility, the Research Computing group at Harvard Medical School, and the Boston Children’s Hospital Intellectual and Developmental Disabilities Research Center Molecular Genetics Core for assistance. Human tissue was obtained from the NIH Neurobiobank at the University of Maryland, and we thank the donors and families for their invaluable contributions to the advancement of science. This work was supported by the Bioinformatics and Integrative Genomics training grant (no. T32HG002295 to L.J.L.), grant nos. K08 AG065502 and T32 HL007627 (to M.B.M.), the Brigham and Women’s Hospital Program for Interdisciplinary Neuroscience through a gift from Lawrence and Tiina Rand (to M.B.M.), the donors of the Alzheimer’s Disease Research program of the BrightFocus Foundation (no. A20201292F to M.B.M.), the Doris Duke Charitable Foundation Clinical Scientist Development Award (no. 2021183 to M.B.M.), PRMRP Discovery Award (no. W81XWH2010028 to Z.Z.), the Edward R. and Anne G. Lefler Center postdoctoral fellowship (to Z.Z.), and grant nos. R00 AG054748 (to M.A.L.), R01 AG070921 (to C.A.W.) and R01NS032457 and U01MH106883 (to P.J.P. and C.A.W.), and the Allen Discovery Center program, a Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation (to C.A.W.). C.A.W. is an investigator at the Howard Hughes Medical Institute. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Funding Information: We thank R. S. Hill, R. Mathieu and L. (Sahithi) Cheemalamarri at the Boston Children’s Hospital & Harvard Stem Cell Institute Flow Cytometry Research Facility, the Research Computing group at Harvard Medical School, and the Boston Children’s Hospital Intellectual and Developmental Disabilities Research Center Molecular Genetics Core for assistance. Human tissue was obtained from the NIH Neurobiobank at the University of Maryland, and we thank the donors and families for their invaluable contributions to the advancement of science. This work was supported by the Bioinformatics and Integrative Genomics training grant (no. T32HG002295 to L.J.L.), grant nos. K08 AG065502 and T32 HL007627 (to M.B.M.), the Brigham and Women’s Hospital Program for Interdisciplinary Neuroscience through a gift from Lawrence and Tiina Rand (to M.B.M.), the donors of the Alzheimer’s Disease Research program of the BrightFocus Foundation (no. A20201292F to M.B.M.), the Doris Duke Charitable Foundation Clinical Scientist Development Award (no. 2021183 to M.B.M.), PRMRP Discovery Award (no. W81XWH2010028 to Z.Z.), the Edward R. and Anne G. Lefler Center postdoctoral fellowship (to Z.Z.), and grant nos. R00 AG054748 (to M.A.L.), R01 AG070921 (to C.A.W.) and R01NS032457 and U01MH106883 (to P.J.P. and C.A.W.), and the Allen Discovery Center program, a Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation (to C.A.W.). C.A.W. is an investigator at the Howard Hughes Medical Institute. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
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