Systematic tracking of altered modules identifies disrupted pathways in teratozoospermia

Area of Science:

• Genomics and Bioinformatics
• Molecular Biology
• Reproductive Medicine

Background:

• Teratozoospermia, characterized by abnormal sperm morphology, significantly impacts male fertility.
• Understanding the molecular mechanisms underlying teratozoospermia is crucial for developing effective diagnostic and therapeutic strategies.

Purpose of the Study:

• To identify disrupted biological pathways in teratozoospermia using reweighted protein-protein interaction (PPI) networks.
• To uncover potential diagnostic biomarkers and therapeutic targets for teratozoospermia.

Main Methods:

• Inferred and reweighted PPI networks for normal and teratozoospermia groups using Spearman correlation coefficients.
• Identified altered modules via clique-merging and maximum weight bipartite matching algorithms.
• Performed pathway-enrichment analysis using DAVID on genes within altered modules.

Main Results:

• Screened 20,102 genes and identified 875 altered modules between normal and teratozoospermia PPI networks.
• Enriched genes in altered modules were associated with 71 pathways, with the cell cycle pathway notably disrupted.
• Identified 36 mutual enriched pathways across different conditions, highlighting key molecular disruptions.

Conclusions:

• The study presents a novel platform for biomarker discovery in teratozoospermia by tracking dysregulated modules in PPI networks.
• Uncovered potential diagnostic and therapeutic targets, paving the way for improved monitoring and treatment of teratozoospermia.
• Highlights the critical role of cell cycle pathway disruption in the progression of teratozoospermia.