Should we build single-cell lineage trees from gene expression data?

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ID: 321547
2026
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Abstract
Abstract Gene expression data has been proposed as a natural single-cell lineage marker. Here, we critically examine the feasibility of reconstructing lineage trees from single-cell transcriptomic data using both modelling and empirical data. We first introduce a notion of neutrality for transcriptomic data, and then, under a model for neutral gene expression, establish theoretical bounds for accurate lineage tree reconstruction. Our findings indicate that reconstruction guarantees for even small trees or sub-trees require thousands of independent, neutral traits – a condition that is likely rarely met in practice due to the dominance of non-neutral developmental signals. Furthermore, errors introduced by measurement sampling have the potential to destroy any existing lineage signal. We conclude that gene expression data has limited potential as a natural lineage recorder and should not be used for phylogenetic lineage tree inference without further, rigorous validation.
Reference Key
openalex_W7169673079 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Nicola Mulberry, Tanja Stadler
Journal current genetics
Year 2026
DOI
10.1093/genetics/iyag187
URL
https://doi.org/10.1093/genetics/iyag187
Keywords Keywords not found

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