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Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
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Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
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Finding spatially variable ligand-receptor interactions with functional support from downstream genes.

Shiying Li1, Ruohan Wang1, Sitong Liu1

  • 1Department of Computer Science, City University of Hong Kong, Hong Kong, China.

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Summary
This summary is machine-generated.

SPIDER identifies spatially variable ligand-receptor interactions (LRIs) using spatial transcriptomics. This method accurately reveals cell-cell communication patterns and their biological significance in complex tissues.

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Area of Science:

  • Genomics
  • Computational Biology
  • Systems Biology

Background:

  • Spatial transcriptomics enables studying intercellular ligand-receptor interactions (LRIs) with spatial context.
  • Identifying spatially variable LRIs is crucial for understanding tissue organization and function.

Purpose of the Study:

  • To present SPIDER, a novel computational framework for identifying spatially variable LRIs with activation evidence.
  • To develop a method that profiles and identifies spatially variable interaction (SVI) signals.

Main Methods:

  • SPIDER constructs cell-cell interaction interfaces based on cellular interaction capacity.
  • It employs multiple probabilistic models to identify SVI signals supported by downstream transcription factors.
  • The method is validated using simulations and real datasets at bulk and single-cell resolutions.

Main Results:

  • SPIDER demonstrates superior accuracy, specificity, and spatial variance compared to existing methods.
  • Validated SVIs show spatial autocorrelation and correlation with downstream target genes across biological replicates.
  • Distinct SVIs in mouse datasets highlight regional and inter-cell type interactions.

Conclusions:

  • SPIDER effectively identifies and characterizes spatially variable ligand-receptor interactions.
  • The framework groups SVIs into patterns, revealing interaction-based sub-clusters and enriched pathways within cell-type regions.