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Related Experiment Video

Updated: May 21, 2026

An Optogenetic Method to Control and Analyze Gene Expression Patterns in Cell-to-cell Interactions
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Inferring stochastic dynamics by biophysical Neural ODE using single-cell transcriptomics.

Jingyu Dou1,2, Wentao Lyu2, Feng Chen1

  • 1Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.

Nature Communications
|May 19, 2026
PubMed
Summary
This summary is machine-generated.

DynNet, a novel deep learning method, infers gene regulatory dynamics for cell fate decisions from single-cell data. It overcomes limitations of existing models, accurately reconstructing cell state transitions and developmental trajectories.

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Area of Science:

  • Computational Biology
  • Systems Biology
  • Genomics

Background:

  • Single-cell RNA sequencing (scRNA-seq) enables cellular heterogeneity analysis but inferring dynamic processes from static data is challenging.
  • Existing computational models for cell fate decisions involve a trade-off between biological realism and interpretability.
  • Understanding gene regulatory dynamics is crucial for dissecting cell fate decisions and developmental processes.

Purpose of the Study:

  • To develop a deep learning framework, DynNet, that integrates Neural Ordinary Differential Equations (Neural ODEs) with biophysical models and prior knowledge.
  • To accurately infer stochastic gene regulatory dynamics governing cell fate decisions from scRNA-seq data.
  • To overcome the limitations of current mechanistic and data-driven approaches in modeling cellular dynamics.

Main Methods:

  • DynNet integrates Neural ODEs with biophysical models and prior knowledge of gene expression.
  • The method learns the stochastic dynamics of gene regulatory systems for cell fate decisions.
  • Benchmarking was performed on synthetic datasets and real biological data (hepatocyte differentiation and EMT).

Main Results:

  • DynNet successfully infers stable cell states and reconstructs dynamical trajectories from static scRNA-seq data.
  • The method characterizes multi-stable cell fate transitions and quantifies transition probabilities.
  • Application to hepatocyte differentiation and EMT data revealed developmental trajectories, cell fate landscapes, and critical gene regulations.

Conclusions:

  • DynNet provides a powerful, interpretable deep learning approach for inferring gene regulatory dynamics and cell fate landscapes from scRNA-seq data.
  • The method advances our understanding of cellular heterogeneity and cell fate decisions in developmental and disease contexts.
  • DynNet offers a promising tool for dissecting complex biological processes at the single-cell level.