Multi-omics integration analysis based on plasma circulating proteins reveals potential therapeutic targets for...

Area of Science:

• Gastroenterology
• Immunology
• Genomics

Background:

• Ulcerative colitis (UC) is a complex inflammatory bowel disease with unknown causes and difficult molecular mechanisms.
• Accurate diagnosis and effective treatment strategies for UC remain challenging.

Purpose of the Study:

• To identify potential diagnostic and therapeutic biomarkers for UC using multi-omics data integration.
• To gain new insights into the precise diagnosis and treatment of UC.

Main Methods:

• Integrated Gene Expression Omnibus and protein quantitative trait loci data to find overlapping genes.
• Employed machine learning algorithms to screen core hub genes and construct a diagnostic model.
• Validated findings using single-cell sequencing, immune infiltration analysis, and a DSS-induced UC mouse model.

Main Results:

• Identified 168 plasma proteins causally associated with UC and 12 overlapping genes.
• Discovered four core hub genes (EIF5A2, IDO1, CDH5, MYL5) with strong predictive performance for UC diagnosis.
• Revealed significant differences in immune cell infiltration and constructed a regulatory network, validated in a mouse model.

Conclusions:

• Systematically identified core diagnostic genes and their regulatory networks for UC through multi-omics integration.
• The identified genes and networks offer potential for precise diagnosis and targeted therapy development for UC.