title: Transcriptomic network analysis of micronuclei-related genes: a case study.
abstract: Mechanistically relevant information on responses of humans to xenobiotic exposure in relation to chemically induced biological effects, such as micronuclei (MN) formation can be obtained through large-scale transcriptomics studies. Network analysis may enhance the analysis and visualisation of such data. Therefore, this study aimed to develop a 'MN formation' network based on a priori knowledge, by using the pathway tool MetaCore. The gene network contained 27 genes and three gene complexes that are related to processes involved in MN formation, e.g. spindle assembly checkpoint, cell cycle checkpoint and aneuploidy. The MN-related gene network was tested against a transcriptomics case study associated with MN measurements. In this case study, transcriptomic data from children and adults differentially exposed to ambient air pollution in the Czech Republic were analysed and visualised on the network. Six genes from the network, i.e. BAX, DMNT1, PCNA, HIC1, p21 and CDC20, were retrieved. Based on these six genes and in combination with p53 and IL-6, a dedicated network was created. This dedicated network is possibly suited for the development of a reporter gene assay that could be used to screen populations complementary to the current MN test assay. In conclusion, we have shown that network analysis of transcriptomics data in relation to the formation of MN is possible and provides a novel mechanistic hypothesis by indicating which genes are regulated and influence others.
authors.affiliation: Department of Health Risk Analysis and Toxicology, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: D M
authors.initials: DM
authors.lastname: van Leeuwen
authors.forename: M
authors.initials: M
authors.lastname: Pedersen
authors.forename: L E
authors.initials: LE
authors.lastname: Knudsen
authors.forename: S
authors.initials: S
authors.lastname: Bonassi
authors.forename: M
authors.initials: M
authors.lastname: Fenech
authors.forename: J C S
authors.initials: JC
authors.lastname: Kleinjans
authors.forename: D G J
authors.initials: DG
authors.lastname: Jennen
mesh_terms: D000328:Adult; D000397:Air Pollution; D002648:Child; D002675:Child, Preschool; D004781:Environmental Exposure; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D015262:Xenobiotics