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Updated: May 14, 2025

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Dissecting multilayer cell-cell communications with signaling feedback loops from spatial transcriptomics data.

Lulu Yan1, Jinyu Cheng2, Qing Nie3

  • 1School of Mathematics, Sun Yat-sen University, Guangzhou 510275, China.

Genome Research
|April 22, 2025
PubMed
Summary
This summary is machine-generated.

Spatial transcriptomics (ST) reveals complex cell-cell communication (CCC). Our new method, stMLnet, integrates spatial data to identify multilayer signaling feedback loops, improving inference of intercellular and intracellular communication pathways.

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Area of Science:

  • Computational Biology
  • Genomics
  • Systems Biology

Background:

  • Spatial transcriptomics (ST) offers novel insights into cellular interactions.
  • Inferring functional cell-cell communication (CCC) from ST data, considering spatial context and signaling, remains challenging.

Purpose of the Study:

  • To introduce stMLnet, a computational method for identifying multilayer signaling feedback loops in CCC from ST data.
  • To leverage spatial information and multilayer signaling regulation for enhanced CCC inference.

Main Methods:

  • stMLnet quantifies spatially dependent ligand-receptor signaling activity using diffusion and mass action models.
  • The method maps intercellular signaling to intracellular targets.
  • Benchmarking against seven methods assessed intercellular ligand-receptor inference and intracellular target gene prediction.

Main Results:

  • stMLnet demonstrated superior performance in both intercellular ligand-receptor inference and intracellular target gene prediction compared to existing methods.
  • The method proved robust and scalable across diverse ST datasets (seqFISH+, Slide-seq v2, MERFISH, Stereo-seq) with varying resolutions and gene coverages.
  • stMLnet identified multilayer signaling feedback loops in the inflammatory response within COVID-19 lung tissue ST data.

Conclusions:

  • stMLnet provides an effective tool for dissecting complex ligand/receptor-target regulation and multicellular signaling circuits from ST data.
  • This advancement aids in understanding the mechanistic and functional roles of spatial CCC.
  • The method supports deeper biological insights from spatial transcriptomics studies.