Functional gene network and ontology enrichment analysis of four reported transcriptomic studies on carbon nanotube exposure in C57BL/J6 mice

Ventura, Célia; Vieira, Luís; Sousa-Uva, António; Silva, Maria João

http://hdl.handle.net/10400.18/5911

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Abstract(s)

Carbon nanotubes (CNT) are one of the most widespread classes of manufactured nanomaterials. Although CNT applications offer great societal and economic benefits, their physicochemical properties may cause adverse human health effects. Several studies have demonstrated that some CNT may cause pulmonary inflammation, fibrosis, and bronchioloalveolar hyperplasia, and their similarity with asbestos have raised concern about their carcinogenicity. In the last years, toxicogenomics has been trying to identify unique gene expression profiles related to exposure to CNT that, besides guiding new research, can also be used as biomarkers for biomonitoring purposes. Furthermore, these “omics” studies try to obtain more insightful information on the cellular functional pathways that are affected. In this study, the potential of genomic data was examined through a gene network and ontology enrichment analysis of a set of 41 differentially expressed genes, selected from a literature search focused on transcriptomic studies of C57BL/6 mice exposed to the CNT Mitsui-7®. The majority of the biological processes annotated in the network are cellular regulatory processes, e.g., interleukin-12 biosynthetic process, and the molecular functions are related to receptor binding signalling, e.g., chemokine receptor binding. Accordingly, the network-annotated pathways are cell receptor-induced pathways, e.g., NF-kB signalling. The results highlight the limited concordance among the published data. Nevertheless, their meta-analysis can be a valuable tool to discover unique gene expression patterns, and identify consistent functional pathways involved in lung pathology from CNT exposure. Moreover, this knowledge can allow grouping CNT according to their mode of action, and contribute to a safer CNT design.