CytokineLink

CytokineLink maps and models cytokine-mediated intercellular communication to analyze how cytokines, their receptors, and cell types form cell-cell and cytokine-cytokine metanetworks using integrated RNA-Seq and immunology database evidence.

Key Features:

• Cytokine communication map: Constructs detailed communication maps illustrating interactions between major tissues and blood cell types under homeostatic conditions.
• Data integration: Integrates Human Protein Atlas, enriched consensus RNA-Seq datasets, immuneXpresso, and ImmunoGlobe to assign proteins, receptors, and corresponding cell types based on literature and empirical evidence.
• Metanetwork construction: Defines and constructs two metanetworks: a cell-cell communication network connected by cytokines and a cytokine-cytokine interaction network depicting potential mutual influences among cytokines.
• Disease-state analysis: Applies expression data from disease contexts to reveal perturbations and rewiring of cytokine-mediated signaling pathways.
• Literature curation: Collates prevalent cytokines from the literature to inform network components.

Scientific Applications:

• Immune response network analysis: Elucidates complex dynamics of cytokine interactions and cellular communication in inflammatory and infectious disease contexts.
• Disease perturbation profiling: Identifies rewiring of communication in ulcerative colitis and detects inactive cell types and altered cytokine interactions in COVID-19 following SARS-CoV-2 infection compared with other viruses.
• Therapeutic insight generation: Provides network-level insights that can inform development of interventions targeting cytokine pathways in diseases with dysregulated immune responses.

Methodology:

CytokineLink collates prevalent cytokines from literature, assigns proteins and receptors to specific tissues and cell types using enriched consensus RNA-Seq data, integrates interaction data from Human Protein Atlas, immuneXpresso, and ImmunoGlobe, and constructs metanetworks modeling direct cell-cell interactions via cytokines and indirect cytokine-cytokine interactions.