Abstract
BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease with few treatment options. Current therapies are not fully effective and show highly variable responses. In this regard, large efforts have focused on developing more effective therapeutic strategies. Drug repurposing based on the comparison of gene expression signatures is an effective technique for the identification of new therapeutic approaches. Here we present a drug-repurposing exploratory analysis using gene expression signatures from SLE patients to discover potential new drug candidates and target genes.MethodsWe collected a compendium of gene expression signatures comprising peripheral blood cells and different separate blood cell types from SLE patients. The Lincscloud database was mined to link SLE signatures with drugs, gene knock-down, and knock-in expression signatures. The derived dataset was analyzed in order to identify compounds, genes, and pathways that were significantly correlated with SLE gene expression signatures.ResultsWe obtained a list of drugs that showed an inverse correlation with SLE gene expression signatures as well as a set of potential target genes and their associated biological pathways. The list includes drugs never or little studied in the context of SLE treatment, as well as recently studied compounds.ConclusionOur exploratory analysis provides evidence that phosphoinositol 3 kinase and mammalian target of rapamycin (mTOR) inhibitors could be potential therapeutic options in SLE worth further future testing.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune disease with few treatment options
Analysis of gene expression signatures After careful exploration we found 10 datasets of SLE in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), two of which contained samples from juvenile SLE patients
The analysis of targets common across the list of drugs yielded three sets with similar gene expression signatures that showed significant p values, including topoisomerase II inhibitors, histone deacetylase (HDAC) inhibitors, and protein kinase C (PKC) activators, as well as three groups with negative scores, where we found phosphoinositol 3 kinase (PI3K) inhibitors, cyclin-dependent kinase (CDK) inhibitors, and mammalian target of rapamycin inhibitors
Summary
Systemic lupus erythematosus (SLE) is an autoimmune disease with few treatment options. The widespread use of highthroughput technologies such as gene expression microarrays has enabled access to large collections of gene expression databases that can be exploited for a wide range of applications. In this context, in-silico drugrepurposing analysis based on gene expression data allows us to identify new therapeutic applications for drugs used in other contexts. In-silico drugrepurposing analysis based on gene expression data allows us to identify new therapeutic applications for drugs used in other contexts
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