Our findings indicate that SLE patients can be stratified into 3 subgroups of patients who show different mechanisms of disease progression and are clinically differentiated. Our results have important implications for treatment options, the design of clinical trials, our understanding of the etiology of the disease, and the prediction of severe glomerulonephritis.

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

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IntroductionSystemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren’s syndrome (SjS) are inflammatory systemic autoimmune diseases (SADs) that share several clinical and pathological features. The shared biological mechanisms are not yet fully characterized. The objective of this study was to perform a meta-analysis using publicly available gene expression data about the three diseases to identify shared gene expression signatures and overlapping biological processes.MethodsPreviously reported gene expression datasets were selected and downloaded from the Gene Expression Omnibus database. Normalization and initial preprocessing were performed using the statistical programming language R and random effects model–based meta-analysis was carried out using INMEX software. Functional analysis of over- and underexpressed genes was done using the GeneCodis tool.ResultsThe gene expression meta-analysis revealed a SAD signature composed of 371 differentially expressed genes in patients and healthy controls, 187 of which were underexpressed and 184 overexpressed. Many of these genes have previously been reported as significant biomarkers for individual diseases, but others provide new clues to the shared pathological state. Functional analysis showed that overexpressed genes were involved mainly in immune and inflammatory responses, mitotic cell cycles, cytokine-mediated signaling pathways, apoptotic processes, type I interferon–mediated signaling pathways and responses to viruses. Underexpressed genes were involved primarily in inhibition of protein synthesis.ConclusionsWe define a common gene expression signature for SLE, RA and SjS. The analysis of this signature revealed relevant biological processes that may play important roles in the shared development of these pathologies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0489-x) contains supplementary material, which is available to authorized users.

BackgroundGenetic association studies (GAS) aims to evaluate the association between genetic variants and phenotypes. In the last few years, the number of this type of study has increased exponentially, but the results are not always reproducible due to experimental designs, low sample sizes and other methodological errors. In this field, meta-analysis techniques are becoming very popular tools to combine results across studies to increase statistical power and to resolve discrepancies in genetic association studies. A meta-analysis summarizes research findings, increases statistical power and enables the identification of genuine associations between genotypes and phenotypes. Meta-analysis techniques are increasingly used in GAS, but it is also increasing the amount of published meta-analysis containing different errors. Although there are several software packages that implement meta-analysis, none of them are specifically designed for genetic association studies and in most cases their use requires advanced programming or scripting expertise.ResultsWe have developed MetaGenyo, a web tool for meta-analysis in GAS. MetaGenyo implements a complete and comprehensive workflow that can be executed in an easy-to-use environment without programming knowledge. MetaGenyo has been developed to guide users through the main steps of a GAS meta-analysis, covering Hardy-Weinberg test, statistical association for different genetic models, analysis of heterogeneity, testing for publication bias, subgroup analysis and robustness testing of the results.ConclusionsMetaGenyo is a useful tool to conduct comprehensive genetic association meta-analysis. The application is freely available at http://bioinfo.genyo.es/metagenyo/.Electronic supplementary materialThe online version of this article (10.1186/s12859-017-1990-4) contains supplementary material, which is available to authorized users.