Integrated in silico analysis of transcriptomic alterations in nanoparticle toxicity across human and mouse models

Nanoparticles, due to their exceptional physicochemical properties are used in our day-to-day environment. They are currently not regulated which might lead to increased levels in the biological systems causing adverse effects. However, the overall mechanism behind nanotoxicity remains elusive. Previously, we analysed the transcriptome datasets of copper oxide nanoparticles using in silico tools and identified IL-17, chemokine signaling pathway, and cytokine-cytokine receptor interaction as the key pathways altered. Based on the findings, we hypothesized a common pathway could be involved in transition metal oxide nanoparticles toxicity irrespective of the variables. Further, there could be unique transcriptome changes between metal oxide nanoparticles and other nanoparticles. To accomplish this, the overall transcriptome datasets of nanoparticles consisting of microarray and RNA-Seq were obtained. >90 studies for 17 different nanoparticles, performed in humans, rats, and mice were assessed. After initial screening, 24 mouse studies (with 196 datasets) and 34 human studies (with 200 datasets) were used for further analyses. The common genes that are dysregulated upon NPs exposure were identified for human and mouse datasets separately. Further, an overrepresentation functional enrichment analysis was performed. The common genes, their gene ontology, gene-gene, and protein-protein interactions were assessed. The overall results suggest that IL-17 and its related pathways might be commonly altered in nanoparticle exposure with lung as one of the major organs affected.