Identification of disturbed pathways in heart failure based on Gibbs sampling and pathway enrichment analysis

Area of Science:

• Biomedical research
• Molecular biology
• Cardiovascular science

Background:

• Heart failure (HF) is a complex condition with incompletely understood molecular underpinnings.
• Identifying key molecular pathways is crucial for understanding HF pathogenesis and developing new therapies.

Purpose of the Study:

• To identify significantly disturbed molecular pathways in heart failure (HF) using a novel computational approach.
• To explore the potential of identified pathways as predictive and prognostic markers for HF.

Main Methods:

• Employed Gibbs sampling combined with pathway enrichment analysis to identify differentially expressed molecular functions (DEMFs) and genes (DEGs).
• Statistical analysis focused on the frequency of occurrence of DEGs within DEMFs.
• Pathway enrichment analysis was performed on significant DEGs to identify affected biological pathways.

Main Results:

• Identified six differentially expressed molecular functions (DEMFs) with a possibility threshold of ≥0.8.
• Found 137 differentially expressed genes (DEGs) occurring at least twice within the DEMFs.
• Pathway enrichment analysis revealed eight significant pathways (P < 0.001), with the top five including calcium signaling, arrhythmogenic right ventricular cardiomyopathy, cardiac muscle contraction, hypertrophic cardiomyopathy, and dilated cardiomyopathy.

Conclusions:

• The combined method of Gibbs sampling and pathway enrichment analysis is effective for identifying significant pathways in HF.
• Altered pathways, particularly the calcium signaling pathway and dilated cardiomyopathy, are predicted to play critical roles in HF.
• These pathways represent potential novel predictive and prognostic markers for heart failure.