Submitted to: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Publication Type: Abstract Only
Publication Acceptance Date: 12/21/2007
Publication Date: 2/22/2008
Citation: Tuggle, C.K., Wang, Y.F., Couture, O.P., Qu, L., Uther, J.J., Kuhar, D.J., Lunney, J.K., Nettleton, D., Dekkers, J.C., Bearson, S.M. 2008. Bioinformatic integration of structural and functional genomics data across species to develop porcine inflammatory gene regulatory pathway information. IEEE/ACM Transactions on Computational Biology and Bioinformatics. Interpretive Summary:
Technical Abstract: Integration of structural and functional genomic data across species holds great promise in finding genes controlling disease resistance. We are investigating the porcine gut immune response to infection through gene expression profiling. We have collected porcine Affymetrix GeneChip data from RNA prepared from mesenteric lymph node of swine infected with either Salmonella enterica serovar Typhimurium (ST) or S. Choleraesuis (SC) for 0, 8, 24, 48 or 504 hours post-inoculation (hpi). In total, we identified 2,365 genes with statistical evidence for differential expression (DE; p < 0.01, q < 0.26, fold-change > 2) between at least two time-points. Comparative Gene Ontology analyses revealed that a high proportion of annotated DE genes in both infections are involved in immune and defense responses. Hierarchical clustering of expression patterns and annotations showed that 27% (22 of 83) of the genes upregulated from 8-24 hpi in SC infection are known NFkB targets. Real-time QPCR analyses confirmed 90% of tested genes. We then collected the sequences of human genes orthologous to the DE genes and used TFM-Explorer to identify a set of 52 gene promoters with significant over-representation of NFkB DNA-binding motifs. Eighteen known NFkB target genes are in this list; we hypothesize the remaining 34 genes are un-recognized NFkB targets. Integration of these results and verification of putative target genes will increase our understanding of the porcine response pathways responding to bacterial infection.