Integrative MultiOmics and Machine Learning Reveal Peroxiredoxin 4 as a Critical Hub Governing Mitochondrial...

Area of Science:

• Oral biology and immunology
• Mitochondrial biology
• Inflammatory disease mechanisms

Background:

• Periodontitis is a chronic inflammatory disease causing tooth loss and increasing systemic risks.
• Current treatments manage symptoms but don't resolve underlying pathogenic environments.
• Mitochondrial dysfunction drives periodontitis, but its gene regulation is unclear.

Purpose of the Study:

• To identify immune cell alterations linked to mitochondrial dysfunction in periodontitis.
• To pinpoint key mitochondria-related genes driving periodontitis progression.
• To explore PRDX4 as a potential therapeutic target.

Main Methods:

• Integrated bulk and single-cell RNA sequencing (RNA-seq).
• Applied non-negative matrix factorization (NMF) and weighted gene coexpression network analysis (WGCNA).
• Utilized machine learning, qPCR, immunofluorescence, and a mouse model.

Main Results:

• Peroxiredoxin 4 (PRDX4) identified as a crucial hub gene for mitochondrial homeostasis.
• PRDX4 upregulation correlated with B cell pathways and differentiation in periodontitis.
• PRDX4's role in B cell regulation confirmed in a mouse model.
• Aloe identified as a potential PRDX4 inhibitor.

Conclusions:

• PRDX4 is a key regulator connecting mitochondrial dysfunction to periodontitis.
• Findings offer insights into mitochondria-related genes in disease pathogenesis.
• PRDX4 presents a potential therapeutic target for periodontitis and related complications.