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Artefacts in single-cell mtDNA analyses misinform phylogenies
Nature
volume 656, pages E25–E31 (2026) Cite this article
Matters Arising to this article was published on 19 August 2026
The Original Article was published on 22 January 2024
arising from: C. Weng et al. Nature https://doi.org/10.1038/s41586-024-07066-z (2024).
The identification of somatic mutations through sequencing has enabled the reconstruction of clonal relationships in native human tissues. In a recent study, Weng et al.1 introduced Regulatory Multiomics (transcriptomics and chromatin accessibility) with Deep Mitochondrial Mutation Profiling (ReDeeM), reporting unprecedented resolution of cellular phylogenies from single-cell mitochondrial DNA (mtDNA) variant data. However, we find that common sequencing artefacts substantially distort potential phylogenetic reconstructions, and removal of probable artificial variants yields markedly disparate phylogenetic inferences. Consequently, the study does not provide robust evidence that somatic mtDNA variation alone permits the confident inference of highly resolved cellular phylogenies.
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Data from this work were downloaded from GSE219015, which was previously published1.