Modeling multifunctionality of genes with secondary gene co-expression networks in human brain provides novel disease insights

MotivationCo-expression networks are a powerful gene expression analysis method to study how genes co-express together in clusters with functional coherence that usually resemble specific cell type behaviour for the genes involved. They can be applied to bulk-tissue gene expression profiling and assign function, and usually cell type specificity, to a high percentage of the gene pool used to construct the network. One of the limitations of this method is that each gene is predicted to play a role in a specific set of coherent functions in a single cell type (i.e. at most we get a single <gene, function, cell type> for each gene). We present here GMSCA (Gene Multifunctionality Secondary Co-expression Analysis), a software tool that exploits the co-expression paradigm to increase the number of functions and cell types ascribed to a gene in bulk-tissue co-expression networks.ResultsWe applied GMSCA to 27 co-expression networks derived from bulk-tissue gene expression profiling of a variety of brain tissues. Neurons and glial cells (microglia, astrocytes and oligodendrocytes) were considered the main cell types. Applying this approach, we increase the overall number of predicted triplets <gene, function, cell type> by 46.73%. Moreover, GMSCA predicts that the SNCA gene, traditionally associated to work mainly in neurons, also plays a relevant function in oligodendrocytes.AvailabilityThe tool is available at GitHub,https://github.com/drlaguna/GMSCA as open source software.ImplementationGSMCA is implemented in R.

Impact of dietary zinc oxide nanoparticles on selected serum biomarkers, lipid peroxidation and tissue gene expression of antioxidant enzymes and cytokines in Japanese quail

Background The use of zinc oxide in the form of nanoparticles (ZnO-NPs) is of great benefit due to its potent effectiveness and higher bioavailability compared to zinc oxide. This study aimed to investigate the impact of dietary inclusion of different doses of ZnO-NPs on selected serum biomarkers, lipid peroxidation and tissue gene expression of antioxidant enzymes and cytokines in Japanese quail. Eighty Japanese quails (Coturnix japonica) (45 days old) were randomly divided into four groups (20 birds for each) with 4 replicates (5 birds each). Birds in the first group were fed a basal diet alone and served as a control (C). Birds in groups 2–4 were fed the basal diet supplemented with ZnO-NPs at doses of 15 mg/kg, 30 mg/kg and 60 mg/kg for a period of 60 days. At the end of the experiment, all birds were sacrificed to collect blood in a plain vacutainer, whereas liver and brain tissues were stored frozen at -80 °C. The obtained sera were used for the analysis of selected biochemical parameters, whereas tissue homogenates were used for the estimation of zinc, oxidative stress biomarkers and gene expression of selected antioxidant enzymes and cytokines. Results ZnO-NPs (30 and 60 mg/kg) induced a significant decrease in serum triacylglycerol (TAG) compared to the control. ZnO-NPs did not affect the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin and tissue zinc concentrations but reduced the malondialdehyde (MDA) levels compared to the control. The liver retained a higher zinc concentration than that of brain tissue. In a dose-dependent manner, ZnO-NPs upregulated the mRNA levels of antioxidant enzymes (superoxide dismutase: SOD1; catalase: CAT; glutathione peroxidase-1: GPX 1) and pro-inflammatory cytokines (interferon α: IFN-α; interleukin 6: IL-6) in liver and brain tissues. Conclusion The current study suggests the inclusion of ZnO-NPs, particularly 60 mg/kg, in the diet of Japanese quails to improve antioxidant and immune status.