KEGGlincs

KEGGlincs integrates LINCS gene expression perturbation data with KEGG pathway topologies to quantify how gene knockouts alter signaling relationships in a cell-type–specific manner.

Key Features:

• R/Bioconductor implementation: Implemented as an R/Bioconductor package for programmatic analysis of perturbation and pathway data.
• KOdata companion: Includes the KOdata companion data package providing manually curated KEGG pathway topologies.
• LINCS integration: Leverages LINCS large-scale gene expression profiles for individual gene knockouts across cancer cell lines.
• Pairwise perturbation overlap analysis: Quantifies overlap in deregulated genes between pairs of knockout experiments to infer functional relationships.
• KEGG edge annotation: Programmatically annotates KEGG pathway edges with perturbation-derived metrics.
• Quantitative pathway perturbation measures: Produces quantitative measures of pathway perturbation that reflect changes in gene function rather than expression alone.
• Cytoscape export: Exports annotated networks for visualization and further analysis in Cytoscape.
• Cell-type–specific assessment: Enables assessment of pathway heterogeneity across cancer cell lines in a cell-type–specific manner.

Scientific Applications:

• Inference of functional relationships: Inferring functional relationships between KEGG pathway components from knockout-induced deregulation overlap.
• Pathway heterogeneity analysis: Assessing heterogeneity of signaling relationships across cell types and cancer cell lines.
• Mechanistic interpretation: Revealing mechanistic insights into biochemical signaling by integrating KEGG topology with LINCS perturbation data.

Methodology:

KEGGlincs uses LINCS knockout gene expression profiles across cancer cell lines, computes overlap in deregulated genes between knockout pairs, programmatically annotates KEGG pathway edges with perturbation-derived quantitative metrics, and uses the KOdata package for curated KEGG pathway topologies; annotated networks can be exported to Cytoscape.