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Related Concept Videos

Diversity in Cell Signaling Responses01:22

Diversity in Cell Signaling Responses

The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
Graded and Abrupt Responses
Some signaling systems generate...
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...

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Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization
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Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization

Published on: October 3, 2025

PathwayEmbed: a computational tool to quantify intracellular signaling transduction states from transcriptomic data.

Yaqing Huang1,2,3, Sharon Gerecht3, Themis Kyriakides1,2

  • 1Department of Pathology, Yale University, New Haven, CT 06520, United States.

Bioinformatics (Oxford, England)
|May 28, 2026
PubMed
Summary
This summary is machine-generated.

PathwayEmbed is a new R framework that quantifies intracellular signaling pathway activity from single-cell transcriptomics. It provides a mechanistic approach to understand cell signaling dynamics and spatial variations.

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Area of Science:

  • Computational Biology
  • Systems Biology
  • Molecular Biology

Background:

  • Intracellular signaling pathways are crucial for cellular functions but difficult to quantify dynamically.
  • Current single-cell omics tools often lack mechanistic insights into signaling directionality.
  • A computational gap exists in precisely measuring signal transduction states.

Purpose of the Study:

  • To develop PathwayEmbed, an R-based computational framework for estimating intracellular signal transduction states.
  • To provide a mechanistically informed method for quantifying and comparing signaling activity in single cells.
  • To address the limitations of existing tools in capturing directional transcriptional changes.

Main Methods:

  • PathwayEmbed integrates KEGG pathway information with RNA sequencing data.
  • Directional coefficients are assigned to capture gene-specific responses to pathway modulation.
  • Cellular states are mapped to a continuous ON/OFF range for each pathway, generating activity scores.

Main Results:

  • PathwayEmbed computes continuous, interpretable single-cell signaling activity scores.
  • The framework enables robust visualization and quantitative comparison of pathway activity across populations.
  • It accurately captures spatial variations in signaling states from spatial transcriptomic data.

Conclusions:

  • PathwayEmbed offers a flexible, mechanistically informed approach for analyzing intracellular signaling.
  • The R package is compatible with existing single-cell workflows and supports user-defined pathways.
  • It facilitates comparisons of signaling activity across temporal and spatial scales.