Single-cell somatic copy number variants in brain using different amplification methods and reference genomes.

Autor:	Kalef-Ezra E; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815., Turan ZG; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815., Perez-Rodriguez D; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK., Bomann I; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK., Behera S; Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston TX 77030, USA., Morley C; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK., Scholz SW; Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA., Jaunmuktane Z; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815.; Queen Square Brain Bank for Neurological disorders, UCL Queen Square Institute of Neurology, London, UK., Demeulemeester J; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815.; Department of Oncology, KU Leuven, Leuven, Belgium.; Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.; VIB Center for Cancer Biology, Leuven, Belgium., Sedlazeck FJ; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815.; Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston TX 77030, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, TX, USA.; Department of Computer Science, Rice University, 6100 Main Street, Houston, TX, USA., Proukakis C; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 21. Date of Electronic Publication: 2023 Nov 21.
DOI:	10.1101/2023.08.07.552289
Abstrakt:	The presence of somatic mutations, including copy number variants (CNVs), in the brain is well recognized. Comprehensive study requires single-cell whole genome amplification, with several methods available, prior to sequencing. We compared PicoPLEX with two recent adaptations of multiple displacement amplification (MDA): primary template-directed amplification (PTA) and droplet MDA, across 93 human brain cortical nuclei. We demonstrated different properties for each, with PTA providing the broadest amplification, PicoPLEX the most even, and distinct chimeric profiles. Furthermore, we performed CNV calling on two brains with multiple system atrophy and one control brain using different reference genomes. We found that 38% of brain cells have at least one Mb-scale CNV, with some supported by bulk sequencing or single-cells from other brain regions. Our study highlights the importance of selecting whole genome amplification method and reference genome for CNV calling, while supporting the existence of somatic CNVs in healthy and diseased human brain. Competing Interests: Competing interests SWS received research support from Cerevel Therapeutics. SWS is a member of the scientific advisory board of the Lewy Body Dementia Association and the Multiple System Atrophy Coalition. FJS receives research support from Genentech, Illumina, PacBio and Oxford Nanopore. All other authors declare no competing interests.
Databáze:	MEDLINE
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