Kalef-Ezra, EsterTuran, Zeliha GozdePerez-Rodriguez, DiegoBomann, IdaBehera, SairamMorley, CaoimheScholz, Sonja W.Jaunmuktane, ZaneDemeulemeester, JonasSedlazeck, Fritz J.Proukakis, Christos2024-11-042024-11-042024Kalef-Ezra, E., Turan, Z. G., Perez-Rodriguez, D., Bomann, I., Behera, S., Morley, C., Scholz, S. W., Jaunmuktane, Z., Demeulemeester, J., Sedlazeck, F. J., & Proukakis, C. (2024). Single-cell somatic copy number variants in brain using different amplification methods and reference genomes. Communications Biology, 7(1), 1–10. https://doi.org/10.1038/s42003-024-06940-whttps://hdl.handle.net/1911/118003The 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.engExcept where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.Journal articles42003-024-06940-whttps://doi.org/10.1038/s42003-024-06940-w