Meta-analysis of crowdsourced data compendia suggests pan-disease transcriptional signatures of autoimmunity

对众包数据汇编的荟萃分析表明,自身免疫性疾病存在泛疾病转录特征

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Abstract

Background: The proliferation of publicly accessible large-scale biological data together with increasing availability of bioinformatics tools have the potential to transform biomedical research. Here we report a crowdsourcing Jamboree that explored whether a team of volunteer biologists without formal bioinformatics training could use OMiCC, a crowdsourcing web platform that facilitates the reuse and (meta-) analysis of public gene expression data, to compile and annotate gene expression data, and design comparisons between disease and control sample groups. Methods: The Jamboree focused on several common human autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), type I diabetes (DM1), and rheumatoid arthritis (RA), and the corresponding mouse models. Meta-analyses were performed in OMiCC using comparisons constructed by the participants to identify 1) gene expression signatures for each disease (disease versus healthy controls at the gene expression and biological pathway levels), 2) conserved signatures across all diseases within each species (pan-disease signatures), and 3) conserved signatures between species for each disease and across all diseases (cross-species signatures). Results: A large number of differentially expressed genes were identified for each disease based on meta-analysis, with observed overlap among diseases both within and across species. Gene set/pathway enrichment of upregulated genes suggested conserved signatures (e.g., interferon) across all human and mouse conditions. Conclusions: Our Jamboree exercise provides evidence that when enabled by appropriate tools, a "crowd" of biologists can work together to accelerate the pace by which the increasingly large amounts of public data can be reused and meta-analyzed for generating and testing hypotheses. Our encouraging experience suggests that a similar crowdsourcing approach can be used to explore other biological questions.

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