Approximate Bayesian computation for inferring Waddington landscapes from single-cell data

Autor: Yujing Liu, Stephen Y. Zhang, Istvan T. Kleijn, Michael P. H. Stumpf
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Royal Society Open Science, Vol 11, Iss 7 (2024)
Druh dokumentu: article
ISSN: 2054-5703
DOI: 10.1098/rsos.231697
Popis: Single-cell technologies allow us to gain insights into cellular processes at unprecedented resolution. In stem cell and developmental biology snapshot data allow us to characterize how the transcriptional states of cells change between successive cell types. Here, we show how approximate Bayesian computation (ABC) can be employed to calibrate mathematical models against single-cell data. In our simulation study, we demonstrate the pivotal role of the adequate choice of distance measures appropriate for single-cell data. We show that for good distance measures, notably optimal transport with the Sinkhorn divergence, we can infer parameters for mathematical models from simulated single-cell data. We show that the ABC posteriors can be used (i) to characterize parameter sensitivity and identify dependencies between different parameters and (ii) to construct representations of the Waddington or epigenetic landscape, which forms a popular and interpretable representation of the developmental dynamics. In summary, these results pave the way for fitting mechanistic models of stem cell differentiation to single-cell data.
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