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Srilakshmi Sharma, Sarah Wheelan, Luigi Marchionni, Christina A. Harrington, Dongseok Choi, Stephen R Planck, James T Rosenbaum; Identification of a gene expression profile specific to non infectious uveitis using high throughput microarray data and a novel pipeline of in-silico methods. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1719.
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© ARVO (1962-2015); The Authors (2016-present)
Microarray technology presents opportunities to study etiological or genetic commonalities within ocular manifestations of heterogenous diseases. Our aims are to characterise gene expression in active uveitis of distinct etiologies and as single heterotype and to develop a novel in-silico pipeline of orthogonal analyses translatable to other diseases.
Gene expression was assayed in the OHSU Gene Microarray Shared Resource using Affymetrix Hu U133 Plus 2.0 Microarray chips on peripheral whole blood samples from active uveitis compared with inactive uveitis for separate etiologies and as a combined class of heterogeneous aetiologies. We studied 35 subjects with active noninfectious (NIU) uveitis, 28 inactive NIU in Ankylosing Spondylitis (AS), Sarcoidosis, Idiopathic Uveitis, Behcets Disease and 25 healthy controls. We developed an in-silico pipeline including frozen Robust Multi-array Average normalisation, Linear Model for Microarray in 'R', differential gene expression identification. False discovery rate <5% defined significance. Methods for downstream analysis included Gene Set enrichment Analysis , Ingenuity Pathway Analysis modules, Panther and text-mining literature search.
TOLL, RIG-1 and NOD, IL21 and Integrin pathways were enriched in subjects with active uveitis. Functional distinctions between individual uveitis aetiologies are present: IL4 pathway is downregulated in Idiopathic uveitis; IL12, p53, IL17/23 pathways are upregulated and wnt-catenin, integrin pathways downregulated. The IL2 pathway is downregulated in AS Uveitis. We identified 13 (3.5 %) DEGs concordant between active uveitis disease classes, e.g., secretory leukocyte peptidase inhibitor & peroxisomal proliferator-activated receptor A (PPAR) interacting complex 285.
Combining multiple analysis modalities enables discovery of genes and pathways shared among heterogeneous diseases & potentially specific to a single clinical features in these diseases. We were able to identify both a common mRNA profile associated with active uveitis in various diseases in peripheral blood and show that each uveitis phenotype is associated with functional relationships distinct from systemic disease and other uveitides.
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