PathwayKO: An integrated platform for deciphering the systems-level signaling pathways.

Area of Science:

• Systems biology and immunology
• Bioinformatics and computational biology

Background:

• Characterizing immune responses in health, disease, and clinical interventions is critical.
• Gene knockout (KO) transcriptomes are vital for understanding impaired signaling pathways.
• There is a need for integrated platforms for systems-level pathway analysis.

Purpose of the Study:

• To introduce the PathwayKO platform for integrative pathway analysis of gene knockout transcriptomes.
• To demonstrate PathwayKO's capability in deciphering target KO signaling pathways at a systems-level.
• To evaluate PathwayKO's performance in assessing pathway analysis methods.

Main Methods:

• PathwayKO integrates pathway enrichment, statistical, and visualization analyses.
• The platform was used to analyze mouse KO transcriptomes from liver resection and sepsis models.
• Model-based assessments were employed to evaluate pathway analysis method performance.

Main Results:

• PathwayKO successfully analyzed mouse KO transcriptomes, revealing immune mechanisms in liver injury and sepsis.
• Both conditions converged on a core set of 21 MyD88-associated signaling pathways.
• Identified pathways include Toll-like receptor, NFκB, MAPK, and PD-1/PD-L1 signaling.

Conclusions:

• The findings suggest common fundamental mechanisms underlying innate immune responses.
• These insights may guide therapeutic strategies for intensive care unit patients.
• Advances in systems-level analysis benefit bioinformatics and systems immunology.