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Inferring differential dynamics from multi-lineage, multi-omic, and multi-sample single-cell data with MultiVeloVAE.

Chen Li1, Yichen Gu2, Maria C Virgilio1,3

  • 1Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.

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|November 20, 2025
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Summary
This summary is machine-generated.

This study introduces MultiVeloVAE, a new computational tool for analyzing single-cell multi-omic data to understand cell differentiation dynamics. It offers novel insights into gene expression and chromatin accessibility during development.

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Area of Science:

  • Biomedical Science
  • Computational Biology
  • Genomics

Background:

  • Cell differentiation is crucial for understanding specialized cell fates.
  • Single-cell multi-omic profiling offers insights into dynamic molecular changes.
  • Existing RNA velocity methods struggle with multi-lineage, multi-sample, and multi-omic single-cell data.

Purpose of the Study:

  • To develop a computational framework for multi-sample RNA velocity inference using integrated single-cell RNA and multi-omic data.
  • To address limitations of previous methods in handling complex single-cell datasets.
  • To enable the identification of differential molecular dynamics during cell differentiation.

Main Methods:

  • Introduced MultiVeloVAE, a probabilistic framework for RNA velocity inference.
  • Integrated single-cell RNA and multi-omic data (gene expression and chromatin accessibility).
  • Modeled dynamics on a shared time scale, handling lineage bifurcations and multi-sample inference.

Main Results:

  • MultiVeloVAE successfully models gene expression and chromatin accessibility dynamics.
  • The framework supports multi-sample inference from datasets with partially overlapping modalities.
  • Demonstrated novel insights into chromatin accessibility and gene expression dynamics using human embryoid body and macrophage differentiation data.

Conclusions:

  • MultiVeloVAE overcomes limitations of previous RNA velocity methods for complex single-cell data.
  • The framework provides a powerful tool for analyzing multi-omic single-cell data to study cell differentiation.
  • Offers new understanding of molecular dynamics during human development and cell specialization.