Identifying Common Diagnostic Biomarkers and Therapeutic Targets between COPD and Sepsis: A Bioinformatics and...

Area of Science:

• Genomics
• Immunology
• Computational Biology

Background:

• Chronic obstructive pulmonary disease (COPD) and sepsis share a bidirectional association with unclear underlying mechanisms.
• Understanding the interplay between COPD and sepsis is crucial for developing effective treatments.
• Existing research lacks comprehensive analysis of shared genetic factors and immune involvement.

Purpose of the Study:

• To investigate shared diagnostic genes and potential mechanisms linking COPD and sepsis.
• To explore the role of immune cells in the COPD-sepsis relationship.
• To identify potential therapeutic drugs for COPD and sepsis.

Main Methods:

• Utilized two-sample Mendelian randomization (MR) analysis with genome-wide association data for COPD and sepsis.
• Employed differential gene expression (DEG) analysis and weighted gene co-expression network analysis (WGCNA) to identify common genes.
• Applied LASSO and SVM-RFE algorithms for diagnostic gene identification, alongside immune cell infiltration analysis (CIBERSORT) and network construction.

Main Results:

• Identified three immune cell types mediating the COPD-sepsis relationship, with specific percentage contributions.
• Discovered 33 overlapping genes, highlighting AIM2 and RNF125 as key diagnostic genes.
• Revealed dysregulation in monocytes, macrophages, plasma cells, and dendritic cells, with ten potential drug targets identified and seven validated.

Conclusions:

• AIM2 and RNF125 show promise as diagnostic biomarkers for the COPD-sepsis link.
• Specific immune cell subsets are implicated as mediators in the COPD-sepsis connection.
• The study provides insights into potential therapeutic strategies targeting identified genes and immune pathways.