Introduction

  • The study of cell-cell communication primarily investigates the mechanisms by which a cell transmits and receives signals from its environment, as well as within itself.

  • scRNA-seq data inherently encompasses gene expression information, which can be leveraged to deduce these intercellular communications.

Cell Type Annotation

  • The first step for cell-cell communication (CCC) analysis is cell types annotation with SingleR. After that, interested cell types are selected for CCC analysis.

  • In this report, four cell types including B cells, Monocyte, NK Cells and T cells were chosen for this cell-cell communication inference analysis.

Healthy

The UMAP plots show the result of this step with cell type annotation

Dengue Fever (DF) - non-severe

The UMAP plots show the result of this step with cell type annotation

Dengue Hemorrhagic Fever (DHF) - Severe

The UMAP plots show the result of this step with cell type annotation

Inference of cell-cell communication network

Introduce CellChat

  • CellChat predicts major signaling inputs and outputs for cells and how those cells and signals coordinate for functions using network analysis and pattern recognition approaches.

  • CellChat infers the biologically significant cell-cell communication by assigning each interaction with a probability value and peforming a permutation test. CellChat models the probability of cell-cell communication by integrating gene expression with prior known knowledge of the interactions between signaling ligands, receptors and their cofactors using the law of mass action.

  • CellChat starts with the big picture to predict general principles of cell-cell communication. When comparing cell-cell communication among multiple biological conditions, it can answer the following biological questions:

    • Whether the cell-cell communication is enhanced or not

    • The interaction between which cell types is significantly changed

    • How the major sources and targets change from one condition to another

Summary result

Barplot

Bar plots shows the number of interactions or the total interaction strength (weights) amongs groups.

Bar plots shows the number of interactions or the total interaction strength (weights) amongs groups.

Comprehensive circle plot

Circle plots shows the number of interactions of three groups.

Circle plots shows the number of interactions of three groups.

Comparison circle plot HT & DF


Red (or blue) colored edges represent increased(or decreased) signaling in the second dataset compared to the first one.
Circle plots shows the number of interactions or the total interaction strength (weights) between two groups.

Circle plots shows the number of interactions or the total interaction strength (weights) between two groups.

Comparison circle plot HT & DHF


Red (or blue) colored edges represent increased(or decreased) signaling in the second dataset compared to the first one.
Circle plots shows the number of interactions or the total interaction strength (weights) between two groups.

Circle plots shows the number of interactions or the total interaction strength (weights) between two groups.

The reuslt of CCC analysis in detail

Table 1: The table shows all the inferred cell-cell communications at the level of ligands and receptors

Healthy

Dengue Fever (DF) - non-severe

Dengue Hemorrhagic Fever (DHF) - Severe

The aggregated cell-cell communication network

  • The Number of Interactions refers to the count or frequency of interactions between two cell groups.In the circle plot, the thickness or darkness of the lines or arcs connecting the cell groups represents the number of interactions between them. A thicker or darker line indicates a higher number of interactions between the corresponding cell groups.

  • The Total Interaction Strength or “Weights” refers to the cumulative strength or intensity of interactions between two cell groups. It takes into account various factors such as ligand-receptor affinities, signal intensities, and other quantitative measures. In the circle plot, the thickness or darkness of the lines or arcs connecting the cell groups represents the total interaction strength between them. A thicker or darker line indicates a stronger overall interaction between the corresponding cell groups.

Healthy

Circle plots shows the number of interactions or the total interaction strength (weights) between any two cell groups.

Circle plots shows the number of interactions or the total interaction strength (weights) between any two cell groups.

Dengue Fever (DF) - non-severe

Circle plots shows the number of interactions or the total interaction strength (weights) between any two cell groups.

Circle plots shows the number of interactions or the total interaction strength (weights) between any two cell groups.

Dengue Hemorrhagic Fever (DHF) - Severe

Circle plots shows the number of interactions or the total interaction strength (weights) between any two cell groups.

Circle plots shows the number of interactions or the total interaction strength (weights) between any two cell groups.

Examine the signaling sent from each cell group

  • In all visualization plots, edge colors are consistent with the sources as sender, and edge weights are proportional to the interaction strength. Thicker edge line indicates a stronger signal. Circle sizes are proportional to the number of cells in each cell group.

Healthy

B cells
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

Monocyte
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

NK Cells
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

T cells
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

Dengue Fever (DF) - non-severe

B cells
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

Monocyte
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

NK Cells
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

T cells
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

Dengue Hemorrhagic Fever (DHF) - Severe

B cells
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

Monocyte
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

NK Cells
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

T cells
Circle plots shows the total interaction strength (weights) between each cell group to others.

Circle plots shows the total interaction strength (weights) between each cell group to others.

Top 3 pathways have the highest probability

  • Hierarchy plot: The hierarchical plot consist of two components: the left portion shows autocrine and paracrine signaling to certain cell groups of interest and the right portion shows autocrine and paracrine signaling to the remaining cell groups in the dataset. Thus, hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.
  • Chord diagram: The Chord diagram visualizes cell-cell communication between different cell groups (where each sector in the chord diagram is a cell group). In the Chord diagram, the inner thinner bar colors represent the targets that receive signal from the corresponding outer bar. The inner bar size is proportional to the signal strength received by the targets. Such inner bar is helpful for interpreting the complex chord diagram.

Healthy

TGFb pathway
Chord diagram
Chord diagram visualized the cell-cell communication between different cell groups.

Chord diagram visualized the cell-cell communication between different cell groups.

Hierachry plot
Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Circle plot
Circle plot visualizes the inferred communication network of signaling pathways.

Circle plot visualizes the inferred communication network of signaling pathways.

Heatmap
Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Barplot
Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

CCL pathway
Chord diagram
Chord diagram visualized the cell-cell communication between different cell groups.

Chord diagram visualized the cell-cell communication between different cell groups.

Hierachry plot
Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Circle plot
Circle plot visualizes the inferred communication network of signaling pathways.

Circle plot visualizes the inferred communication network of signaling pathways.

Heatmap
Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Barplot
Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

MIF pathway
Chord diagram
Chord diagram visualized the cell-cell communication between different cell groups.

Chord diagram visualized the cell-cell communication between different cell groups.

Hierachry plot
Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Circle plot
Circle plot visualizes the inferred communication network of signaling pathways.

Circle plot visualizes the inferred communication network of signaling pathways.

Heatmap
Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Barplot
Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Dengue Fever (DF) - non-severe

MIF pathway
Chord diagram
Chord diagram visualized the cell-cell communication between different cell groups.

Chord diagram visualized the cell-cell communication between different cell groups.

Hierachry plot
Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Circle plot
Circle plot visualizes the inferred communication network of signaling pathways.

Circle plot visualizes the inferred communication network of signaling pathways.

Heatmap
Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Barplot
Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

GALECTIN pathways
Chord diagram
Chord diagram visualized the cell-cell communication between different cell groups.

Chord diagram visualized the cell-cell communication between different cell groups.

Hierachry plot
Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Circle plot
Circle plot visualizes the inferred communication network of signaling pathways.

Circle plot visualizes the inferred communication network of signaling pathways.

Heatmap
Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Barplot
Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

RESISTIN pathways
Chord diagram
Chord diagram visualized the cell-cell communication between different cell groups.

Chord diagram visualized the cell-cell communication between different cell groups.

Hierachry plot
Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Circle plot
Circle plot visualizes the inferred communication network of signaling pathways.

Circle plot visualizes the inferred communication network of signaling pathways.

Heatmap
Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Barplot
Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Dengue Hemorrhagic Fever (DHF) - Severe

GALECTIN pathways
Chord diagram
Chord diagram visualized the cell-cell communication between different cell groups.

Chord diagram visualized the cell-cell communication between different cell groups.

Hierachry plot
Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Circle plot
Circle plot visualizes the inferred communication network of signaling pathways.

Circle plot visualizes the inferred communication network of signaling pathways.

Heatmap
Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Barplot
Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

MIF pathway
Chord diagram
Chord diagram visualized the cell-cell communication between different cell groups.

Chord diagram visualized the cell-cell communication between different cell groups.

Hierachry plot
Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Circle plot
Circle plot visualizes the inferred communication network of signaling pathways.

Circle plot visualizes the inferred communication network of signaling pathways.

Heatmap
Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Barplot
Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

ANNEXIN pathways
Chord diagram
Chord diagram visualized the cell-cell communication between different cell groups.

Chord diagram visualized the cell-cell communication between different cell groups.

Hierachry plot
Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Hierarchy plot provides an informative and intuitive way to visualize autocrine and paracrine signaling communications between cell groups of interest.

Circle plot
Circle plot visualizes the inferred communication network of signaling pathways.

Circle plot visualizes the inferred communication network of signaling pathways.

Heatmap
Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Heatmap shows the relative importance of each cell group based on the computed four network centrality measures.

Barplot
Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Barplot shows relative contribution of each ligand-receptor pair to the overall communication network .

Explore how multiple cell types and signaling pathways coordinate together

  • Outgoing patterns reveal how the sender cells (i.e. cells as signal source) coordinate with each other as well as how they coordinate with certain signaling pathways to drive communication.

  • Incoming patterns show how the target cells (i.e. cells as signal receivers) coordinate with each other as well as how they coordinate with certain signaling pathways to respond to incoming signals.

Healthy

The inferred outgoing communication patterns
The inferred outgoing communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

The inferred outgoing communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

The inferred incoming communication patterns
The inferred incoming communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

The inferred incoming communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

Dengue Fever (DF) - non-severe

The inferred outgoing communication patterns
The inferred outgoing communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

The inferred outgoing communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

The inferred incoming communication patterns
The inferred incoming communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

The inferred incoming communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

Dengue Hemorrhagic Fever (DHF) - Severe

The inferred outgoing communication patterns
The inferred outgoing communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

The inferred outgoing communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

The inferred incoming communication patterns
The inferred incoming communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

The inferred incoming communication patterns of secreting cells, which shows the correspondence between the inferred latent patterns and cell groups, as well as signaling pathways.

Software Catalog

Analysis Software Version
Cell–Cell Communication Inference CellChat 1.6.1
Cell Type Annotation SingleR 1.8.1