Cell-to-cell communication analytics

This repository contains a reproducible computational workflow for studying cell-to-cell communication (CCC) in the bone marrow tumor microenvironment across Multiple Myeloma (MM) disease progression, using publicly available single-cell RNA sequencing (scRNA-seq) datasets.

Pipeline overview

The pipeline integrates:

1. CellChat network analysis

   • CCC network inference
   • Stage-specific interaction networks
   • Edge lists and rewiring calculation

2. Cytoscape network analytics

   • CytoHubba
     • Basic network topology metrics e.g. Degree centrelity, betweenness centrality, bottlenecks
   • DyNet
     • Differential network rewiring across disease stages

3. NicheNet downstream analsyis

   • Ligand prioritization in sender cells
   • Identification of downstream transcription factors and target genes in receiver cell types
   • Inference of ligand–TF–target regulatory links associated with MM progression

Project goals

This pipeline was designed to:

1. Infer cell-to-cell communication networks in MM progression

2. Identify important cell types via network topology metrics

3. Detect rewired cell-to-cell interactions across disease stages

4. Prioritize ligands, intermediate transcription factors, and downstream target genes associated with progression of the disease

Running the pipeline

1. Input: pre-processed Seurat objects

2. CCC inference with scRANK (CellChat wrapper: runCellChat)

   • CCC networks
   • Edge lists
   • Edge rewiring across stages

3. Network analytics in Cytoscape

   • CytoHubba: identify important cell types via network topology metrics
   • DyNet: detect rewired cell nodes and interactions across stages

4. NicheNet downstream analyses

   • Ligand prioritization in sender cell types
   • Identification of downstream transcription factors and target genes in receiver cell types
   • Ligand-to-target inference for progression-associated signaling

R packages

Main packages used:

• Seurat
• SeuratObject
• scRANK
• tidyverse
• NicheNetR
• ggplot2

Contact

For questions, issues, or collaborations, feel free to open a GitHub issue or contact: Bioinformatics Department, The Cyprus Institute of Neurology and Genetics Eleni Nicolaidou Email: elenin@cing.ac.cy