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Authors defend mitochondrial DNA filtering methods in single-cell phylogeny study

C. Weng, J. S. Weissman and V. G. Sankaran replied to criticism, showing that their variant-filtering strategy for single-cell mtDNA data remains reliable and does not change the original study’s conclusions.

The authors of the original single-cell mitochondrial DNA study addressed concerns about artefacts by conducting extensive re-analyses of their data. Using different alignment tools and applying edge-trimming or a stricter filter2, they observed similar numbers of detected mutations and retained connections among cells. Comparative metrics, such as agreement of closeness and Jaccard distances, remained high and far above random expectations.

Analyses also revealed that allowing 1-molecule mutations can improve specific agreement measures while still supporting robust lineage reconstruction. Overall, the refined filtering approach maintains the integrity of the phylogenetic trees and the biological interpretations drawn from them. The reply emphasizes that the methodological point under debate does not affect the broader experimental design or major biological findings of the original article.

Why it matters

It confirms that key conclusions about cell lineage tracing from single-cell mtDNA data are not compromised by the debated filtering choices.

In this story

mitochondrial DNAsingle-cell sequencingphylogenyvariant filteringReDeeM pipelinefilter2edge trimmingcell lineagemutation callingrobustness
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