Abstract

Recent single-cell analysis technologies offer an unprecedented opportunity to elucidate developmental pathways. Here we present Wishbone, an algorithm for positioning single cells along bifurcating developmental trajectories with high resolution. Wishbone uses multi-dimensional single-cell data, such as mass cytometry or RNA-Seq data, as input and orders cells according to their developmental progression, and it pinpoints bifurcation points by labeling each cell as pre-bifurcation or as one of two post-bifurcation cell fates. Using 30-channel mass cytometry data, we show that Wishbone accurately recovers the known stages of T-cell development in the mouse thymus, including the bifurcation point. We also apply the algorithm to mouse myeloid differentiation and demonstrate its generalization to additional lineages. A comparison of Wishbone to diffusion maps, SCUBA and Monocle shows that it outperforms these methods both in the accuracy of ordering cells and in the correct identification of branch points.

Keywords

Mass cytometryBifurcationGeneralizationComputer scienceBifurcation theoryBiologyAlgorithmMathematicsPhenotypePhysicsGeneticsMathematical analysis

MeSH Terms

AlgorithmsAnimalsCell DifferentiationComputer SimulationMiceModelsBiologicalMorphogenesisSoftwareT-Lymphocytes

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Publication Info

Year
2016
Type
article
Volume
34
Issue
6
Pages
637-645
Citations
617
Access
Closed

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617
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Cite This

Manu Setty, Michelle D. Tadmor, Shlomit Reich-Zeliger et al. (2016). Wishbone identifies bifurcating developmental trajectories from single-cell data. Nature Biotechnology , 34 (6) , 637-645. https://doi.org/10.1038/nbt.3569

Identifiers

DOI
10.1038/nbt.3569
PMID
27136076
PMCID
PMC4900897

Data Quality

Data completeness: 86%