Method

Bayesian inference of lineage trees by joint analysis of single-cell multimodal lineage-tracing data with BiLinT

    • 1Program for Mathematical Genomics, Columbia University, New York, New York 10032, USA;
    • 2Department of Systems Biology, Columbia University, New York, New York 10032, USA;
    • 3Courant Institute of Mathematical Sciences, New York University, New York, New York 10012, USA;
    • 4Department of Epidemiology, Columbia University, New York, New York 10032, USA;
    • 5SKLMS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, China;
    • 6University of Chinese Academy of Sciences, Beijing 100049, China;
    • 7Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
    • 8 These authors contributed equally to this work.
Published August 21, 2026. https://doi.org/10.1101/gr.281460.125
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Abstract

The advent of single-cell lineage-tracing technologies has enabled the simultaneous profiling of gene expression and lineage barcodes. However, accurate, high-resolution reconstruction of cell lineage trees remains challenging because most existing approaches treat these modalities separately and therefore fail to fully exploit their complementary information. Here we present BiLinT, a Bayesian framework that jointly models multimodal single-cell lineage-tracing data for lineage tree reconstruction. BiLinT integrates barcode evolution (a continuous-time Markov chain) with gene expression dynamics (an Ornstein–Uhlenbeck process) within a unified probabilistic model. Across synthetic and real data sets, BiLinT provides accurate lineage-tree reconstruction and reveals differentiation-associated clonal structure and developmental fate biases.

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