Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic, relapsing autoimmune disease affecting multiple organs and is a highly heterogeneous condition, with wide variations in the presentation and severity of disease and the biological markers identified . We analyzed multi-modal biomarker (mRNA, miRNA, cytokines and autoantibodies) data from ~100 clinically annotated SLE patients under standard of care from a single clinical center (Northwell Rheumatology Clinic) along with ~100 NHVs to identify key dysregulated and co-dysregulated markers in SLE.
Methods: To address the issue of heterogeneity, we applied 2 approaches namely outlier analysis  followed by market basket analysis  to identify dysregulated and co-dysregulated markers in this multi-modal biomarker rich dataset. We also used pathway analysis and knowledge databases to assess the biological relevance of these markers.
Results: For the whole blood transcriptomic data, on an average, 13% genes were found to be dysregulated in an SLE patient and ~ 6% of genes were found to be dysregulated in at least 25% of SLE patients (Fig.1). Percentage of outlier genes showed weak correlation with SLEDAI scores . Pathway analysis of outlier genes showed an enrichment for IFN signaling pathways (Fig. 2). Market basket analysis identified several high-confidence (>0.8) co-dysregulated associations across a wide proportion of patients. The IFN genes formed the most promiscuous associations. The high-confidence associations were further prioritized based on multi-modality (e.g. miRNA:mRNA) and opposing regulation.
Conclusion: Several key dysregulated markers were identified in SLE patients using outlier analysis, which might have been otherwise missed by traditional ANOVA-based approaches because of the heterogeneity in patients. Furthermore, the market basket analysis identified several co-dysregulated markers in patient sub-populations which might be missed by traditional co-expression analysis that requires co-dysregulation across all patients. These markers can be drivers and potential patient stratification biomarkers of SLE and might also help to understand the pathophysiology of this heterogeneous and complex disease.
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To cite this abstract in AMA style:Hu YS, Bandyopadhyay S, Carman J, Manjarrez-Orduño N, Jiang C, Suchard S, Menard L, habte S, kansal S, jayaswal V, Furie RA, Nadler SG. Identifying Dysregulated and Co-Dysregulated Markers in Systemic Lupus Erythematosus Using Multi-Modal Biomarker Data from a Large Pre-Clinical Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/identifying-dysregulated-and-co-dysregulated-markers-in-systemic-lupus-erythematosus-using-multi-modal-biomarker-data-from-a-large-pre-clinical-study/. Accessed November 25, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identifying-dysregulated-and-co-dysregulated-markers-in-systemic-lupus-erythematosus-using-multi-modal-biomarker-data-from-a-large-pre-clinical-study/