4.8 Article

DeepVelo: Single-cell transcriptomic deep velocity field learning with neural ordinary differential equations

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SCIENCE ADVANCES
卷 8, 期 48, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abq3745

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资金

  1. NIH
  2. [K01MH123896,1R01HG012572]
  3. [U01DA053628,1R01NS128523]
  4. [UM1DA051410]

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Recent advances in single-cell sequencing technologies have led to new opportunities for studying the gene expression profile and transcriptome dynamics of individual cells. In this study, the authors propose DeepVelo, a neural network-based method that models complex transcriptome dynamics by simulating continuous changes in gene expression over time within cells. DeepVelo was applied to analyze transcriptome dynamics at different time scales and identify developmental driver genes through perturbation analysis.
Recent advances in single-cell sequencing technologies have provided unprecedented opportunities to measure the gene expression profile and RNA velocity of individual cells. However, modeling transcriptional dynamics is computationally challenging because of the high-dimensional, sparse nature of the single-cell gene expression measurements and the nonlinear regulatory relationships. Here, we present DeepVelo, a neural network-based ordinary differential equation that can model complex transcriptome dynamics by describing continuous-time gene expression changes within individual cells. We apply DeepVelo to public datasets from different sequencing platforms to (i) formulate transcriptome dynamics on different time scales, (ii) measure the instability of cell states, and (iii) identify developmental driver genes via perturbation analysis. Benchmarking against the state-of-the-art methods shows that DeepVelo can learn a more accurate representation of the velocity field. Furthermore, our perturbation studies reveal that single-cell dynamical systems could exhibit chaotic properties. In summary, DeepVelo allows data-driven discoveries of differential equations that delineate single-cell transcriptome dynamics.

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