Bioinformatics-Driven New Immune Target Discovery in Disease.

Abstract

Biomolecular network analysis has been widely applied in the discovery of cancer driver genes and molecular mechanism anatomization of many diseases on the genetic level. However, the application of such approach in the potential antigen discovery of autoimmune diseases remains largely unexplored. Here, we describe a previously uncharacterized region, with disease-associated autoantigens, to build antigen networks with three bioinformatics tools, namely NetworkAnalyst, GeneMANIA and ToppGene. First, we identified histone H2AX as an antigen of systemic lupus erythematosus by comparing highly ranked genes from all the built network-derived gene lists, and then a new potential biomarker for Behcet's disease, heat shock protein HSP 90-alpha (HSP90AA1), was further screened out. Moreover, 130 confirmed patients were enrolled and a corresponding enzyme-linked immunosorbent assay, mass spectrum analysis and immunoprecipitation were performed to further confirm the bioinformatics results with real-world clinical samples in succession. Our findings demonstrate that the combination of multiple molecular network approaches is a promising tool to discover new immune targets in diseases.

• Authors: C Yang, P Chen, W Zhang, H Du
• Journal: Scandinavian journal of immunology (Scand J Immunol) Vol. 84 Issue 2 Pg. 130-6 (Aug 2016) ISSN: 1365-3083 [Electronic] England
• PMID: 27226232 (Publication Type: Journal Article)
• Copyright: © 2016 The Foundation for the Scandinavian Journal of Immunology.

Chemical References

• Autoantigens
• HSP90 Heat-Shock Proteins
• HSP90AA1 protein, human
• Histones

Topics

• Adolescent
• Adult
• Aged
• Autoantigens (genetics)
• Behcet Syndrome (genetics)
• Computational Biology
• Female
• Gene Regulatory Networks (immunology)
• HSP90 Heat-Shock Proteins (genetics)
• Histones (genetics)
• Humans
• Lupus Erythematosus, Systemic (genetics)
• Male
• Middle Aged
• Young Adult