Multiomics Integration and Machine Learning Reveal Colony Stimulating Factor 3 Receptor as a Key Gene and Therapeutic...

Area of Science:

• Immunology and Genetics
• Molecular Biology

Background:

• Crohn's disease (CD) is a chronic inflammatory condition with complex immune dysregulation.
• Identifying key molecular drivers is crucial for advancing diagnostic and therapeutic strategies in CD.

Purpose of the Study:

• To identify key molecular drivers in Crohn's disease using integrated transcriptomic data and machine learning.
• To investigate the role of CSF3R in CD pathogenesis and its potential as a diagnostic and therapeutic target.

Main Methods:

• Integrated transcriptomic data analysis using Random Forest, SVM-RFE, and LASSO algorithms.
• Mendelian randomization (MR) analysis to assess the causal role of CSF3R.
• Single-cell RNA sequencing, immune infiltration analysis, qPCR, Western blot, immunohistochemistry, and molecular docking for validation.

Main Results:

• CSF3R was identified as a top candidate gene causally linked to CD pathogenesis (OR = 1.400).
• Elevated CSF3R expression was observed in neutrophils, associated with neutrophil-mediated inflammation.
• Experimental validation confirmed significantly upregulated CSF3R mRNA and protein levels in CD patients; high diagnostic performance (AUC 0.823-0.938) was achieved.

Conclusions:

• CSF3R is a robust diagnostic biomarker for Crohn's disease.
• CSF3R represents a promising therapeutic target, with potential binding affinity to agents like methotrexate and aspirin.
• These findings provide mechanistic insights and support precision medicine approaches for CD.