Integrative transcriptome-wide analysis of atopic dermatitis for drug repositioning

Integrative genomic and transcriptomic analyses on publicly available data-sets together with in silico drug repositioning identifies alternative therapeutic options to treat atopic dermatitis. Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, which significantly impact the quality of life. Transcriptome-wide association study (TWAS) was conducted to estimate both transcriptomic and genomic features of AD and detected significant associations between 31 expression quantitative loci and 25 genes. Our results replicated well-known genetic markers for AD, as well as 4 novel associated genes. Next, transcriptome meta-analysis was conducted with 5 studies retrieved from public databases and identified 5 additional novel susceptibility genes for AD. Applying the connectivity map to the results from TWAS and meta-analysis, robustly enriched perturbations were identified and their chemical or functional properties were analyzed. Here, we report the first research on integrative approaches for an AD, combining TWAS and transcriptome meta-analysis. Together, our findings could provide a comprehensive understanding of the pathophysiologic mechanisms of AD and suggest potential drug candidates as alternative treatment options.

Automated summary

This study applies integrative genomic and transcriptomic analyses, combined with in silico drug repositioning, to identify alternative therapeutic options for treating atopic dermatitis. The study identifies the transcriptionomic and genomic features of atopic dermatitis and replicates known genetic markers while also discovering new associated genes. By conducting a meta-analysis of transcriptomes from multiple studies, additional susceptibility genes are identified. The study then utilizes connectivity mapping to analyze the chemical or functional properties of these genes. This research provides a comprehensive understanding of the pathophysiologic mechanisms of atopic dermatitis and suggests potential alternative drug candidates for treatment.