A meta-analysis of public microarray data identifies gene regulatory pathways deregulated in peripheral blood mononuclear cells from individuals with Systemic Lupus Erythematosus compared to those without

摘要

BACKGROUND: Systemic Lupus Erythematosus (SLE) is a complex, multi-systemic, autoimmune disease for which theunderlying aetiological mechanisms are poorly understood. The genetic and molecular processes underlying lupushave been extensively investigated using a variety of -omics approaches, including genome-wide association studies,candidate gene studies and microarray experiments of differential gene expression in lupus samples compared tocontrols.METHODS: This study analyses a combination of existing microarray data sets to identify differentially regulated geneticpathways that are dysregulated in human peripheral blood mononuclear cells from SLE patients compared to unaffectedcontrols. Two statistical approaches, quantile discretisation and scaling, are used to combine publicly available expressionmicroarray datasets and perform a meta-analysis of differentially expressed genes.RESULTS: Differentially expressed genes implicated in interferon signaling were identified by the meta-analysis,in agreement with the findings of the individual studies that generated the datasets used. In contrast to theindividual studies, however, the meta-analysis and subsequent pathway analysis additionally highlighted TLRsignaling, oxidative phosphorylation and diapedesis and adhesion regulatory networks as being differentiallyregulated in peripheral blood mononuclear cells (PBMCs) from SLE patients compared to controls.CONCLUSION: Our analysis demonstrates that it is possible to derive additional information from publiclyavailable expression data using meta-analysis techniques, which is particularly relevant to research into rarediseases where sample numbers can be limiting.