PathwayKO

PathwayKO performs integrative systems-level analysis of signaling pathways disrupted by gene knockouts to identify altered pathways and mechanisms from high-throughput transcriptome data.

Key Features:

• Integrated Methodologies: Combines pathway enrichment analysis, statistical evaluation, and visualization for analysis of high-throughput transcriptome data from KO experiments.
• Systems-Level Analysis: Characterizes immune landscapes and signaling networks across conditions including health, disease, and clinical interventions.
• Application to Mouse KO Transcriptomes: Analyzes real-world mouse KO transcriptomes, including datasets from non-infectious extensive hepatectomy and CASP-model sepsis.
• Identification of Shared Mechanisms: Detects common signaling pathways across experimental models, including a core set of 21 KO MyD88-associated signaling pathways identified across conditions.
• Model-Based Performance Evaluation: Benchmarks pathway analysis methods using model-based assessments against collections of transcriptomes.

Scientific Applications:

• Systems immunology research: Dissects signaling pathway perturbations and immune response mechanisms caused by gene knockouts.
• Comparative KO analysis: Identifies conserved and condition-specific signaling pathways across mouse KO models such as hepatectomy and CASP-model sepsis.
• MyD88-associated pathway discovery: Characterizes the 21 KO MyD88-associated signaling pathways common to multiple inflammatory conditions.
• Method benchmarking: Supports evaluation and selection of pathway analysis methods by benchmarking against transcriptome collections.
• Translational hypothesis generation: Provides mechanistic insights to inform research strategies aimed at improving outcomes in clinical settings, including intensive care after surgery.

Methodology:

Uses a pipeline integrating pathway enrichment analysis, statistical evaluation, visualization, and model-based assessments for benchmarking against transcriptome collections.