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

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. Here we compare PicoPLEX with two recent adaptations of multiple displa...

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Bibliographic Details
Published in:Communications biology 2024-10, Vol.7 (1), p.1288-10, Article 1288
Main Authors: Kalef-Ezra, Ester, Turan, Zeliha Gozde, Perez-Rodriguez, Diego, Bomann, Ida, Behera, Sairam, Morley, Caoimhe, Scholz, Sonja W., Jaunmuktane, Zane, Demeulemeester, Jonas, Sedlazeck, Fritz J., Proukakis, Christos
Format: Article
Language:English
Subjects:
631/114/1314
631/1647/514/2254
631/208/212
631/378/2583
692/617/375/365
Atrophy
Biomedical and Life Sciences
Brain
Brain - metabolism
Copy number
DNA Copy Number Variations
Genome, Human
Genomes
Humans
Life Sciences
Nucleic Acid Amplification Techniques - methods
Single-Cell Analysis - methods
Whole genome sequencing
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Summary: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. Here we compare 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 demonstrate different properties for each, with PTA providing the broadest amplification, PicoPLEX the most even, and distinct chimeric profiles. Furthermore, we perform CNV calling on two brains with multiple system atrophy and one control brain using different reference genomes. We find that 20.6% 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. Comparison of single cell whole genome amplification methods using human brain nuclei determines suitability for detection of large somatic copy number variants by low coverage whole genome sequencing aligned to different reference genome versions.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-024-06940-w