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Transcriptome Analysis of Single Cells
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Inferring pattern-driving intercellular flows from single-cell and spatial transcriptomics.

Axel A Almet1,2, Yuan-Chen Tsai3,4,5, Momoko Watanabe3,4,5

  • 1Department of Mathematics, University of California, Irvine, Irvine, CA, USA.

Nature Methods
|August 26, 2024
PubMed
Summary
This summary is machine-generated.

FlowSig infers intercellular communication flows from gene expression data. This method reveals how cell signaling drives gene module activity and uncovers complex biological signaling patterns.

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Area of Science:

  • Genomics
  • Systems Biology
  • Computational Biology

Background:

  • Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) provide high-dimensional gene expression data.
  • Gene expression patterns are often described by intercellular communication networks or gene modules, typically assumed to operate independently.
  • Existing methods lack the ability to describe directed intercellular information flows mediated by intracellular gene modules.

Purpose of the Study:

  • To present FlowSig, a novel method for inferring communication-driven intercellular flows from scRNA-seq or ST data.
  • To address the gap in methodologies for describing intercellular signaling dynamics.
  • To analyze how intercellular communication influences intracellular gene module activity.

Main Methods:

  • FlowSig utilizes graphical causal modeling and conditional independence to infer intercellular flows.
  • The method is benchmarked using experimental cortical organoid data and synthetic data from mathematical modeling.
  • Application to diverse biological systems to demonstrate its capabilities.

Main Results:

  • FlowSig successfully infers communication-driven intercellular flows from transcriptomic data.
  • Benchmarking confirms the method's accuracy on both experimental and synthetic datasets.
  • The method captures stimulation-induced paracrine signaling changes in pancreatic islets.
  • FlowSig identifies shifts in intercellular flows associated with COVID-19 severity.
  • Reconstruction of morphogen-driven activator-inhibitor patterns in mouse embryogenesis is achieved.

Conclusions:

  • FlowSig provides a robust framework for dissecting intercellular communication dynamics from gene expression data.
  • The method reveals the interplay between intercellular signaling and intracellular gene modules.
  • FlowSig has broad applicability in understanding various biological processes, from development to disease.