Gene co-expression network analysis identifies porcine genes associated with variation in Salmonella shedding

Abstract

BackgroundSalmonella enterica serovar Typhimurium is a gram-negative bacterium that can colonise the gut of humans and several species of food producing farm animals to cause enteric or septicaemic salmonellosis. While many studies have looked into the host genetic response to Salmonella infection, relatively few have used correlation of shedding traits with gene expression patterns to identify genes whose variable expression among different individuals may be associated with differences in Salmonella clearance and resistance. Here, we aimed to identify porcine genes and gene co-expression networks that differentiate distinct responses to Salmonella challenge with respect to faecal Salmonella shedding.ResultsPeripheral blood transcriptome profiles from 16 pigs belonging to extremes of the trait of faecal Salmonella shedding counts recorded up to 20 days post-inoculation (low shedders (LS), n = 8; persistent shedders (PS), n = 8) were generated using RNA-sequencing from samples collected just before (day 0) and two days after (day 2) Salmonella inoculation. Weighted gene co-expression network analysis (WGCNA) of day 0 samples identified four modules of co-expressed genes significantly correlated with Salmonella shedding counts upon future challenge. Two of those modules consisted largely of innate immunity related genes, many of which were significantly up-regulated at day 2 post-inoculation. The connectivity at both days and the mean gene-wise expression levels at day 0 of the genes within these modules were higher in networks constructed using LS samples alone than those using PS alone. Genes within these modules include those previously reported to be involved in Salmonella resistance such as SLC11A1 (formerly NRAMP1), TLR4, CD14 and CCR1 and those for which an association with Salmonella is novel, for example, SIGLEC5, IGSF6 and TNFSF13B.ConclusionsOur analysis integrates gene co-expression network analysis, gene-trait correlations and differential expression to provide new candidate regulators of Salmonella shedding in pigs. The comparatively higher expression (also confirmed in an independent dataset) and the significantly higher connectivity of genes within the Salmonella shedding associated modules in LS compared to PS even before Salmonella challenge may be factors that contribute to the decreased faecal Salmonella shedding observed in LS following challenge.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-452) contains supplementary material, which is available to authorized users.

Transcriptional profiling of subcutaneous adipose tissue in Italian Large White pigs divergent for backfat thickness

“…Other genes found in the present research and related to inflammatory conditions of the adipose tissue in FAT pigs are particularly interesting to mention: CD163, a member of the scavenger receptor cysteine-rich superfamily (Guo et al 2014;Smith et al 2014); solute carrier family 11 (protoncoupled divalent metal ion transporter), member 1 (SLC11A1), a gene involved in resistance to Salmonella infection (Kommadath et al 2014); chemokine (C-C motif) receptor 1 (CCR1), which was previously found to be overexpressed in obese pigs (Kogelman et al 2014); BCL2-related protein A1 (BCL2A1), a gene found to be overexpressed in pigs with a high obesity index and that is related to immunity, inflammatory pathways and osteoclast differentiation (Kogelman et al 2014); and CD1a molecule (CD1A; indicated as PCD1A in the cited paper), a surface antigen involved in immunity that was found to be overexpressed in obese pigs by Kogelman et al (2014). The same authors highlighted a strong connection between fat deposition on the body (obesity), immunity and bone development.…”

Genome-Wide Analysis and Functional Characterization of the Polyadenylation Site in Pigs Using RNAseq Data

“…Two data sets, ERP004640 and SRP018524, were selected to analyse PAS function under a different androstenone level and salmonella inoculation, respectively2729, including biological replications as well as control and treatment conditions. PAS was first discovered from the two data sets; then, PASs with different usages and their associated genes were identified for gene functional analysis in terms of corresponding conditions (see Materials and Methods).…”

“…The whole blood samples were collected at day 0 and day 2 after the inoculation of pigs with salmonella. A total of 32 RNA libraries were sequenced in 50-bp single-end reads (ERP004640)29.…”

Genomics to benefit livestock production: improving animal health

“…Again, this variation has a genetic component, suggesting it could be possible to improve food safety by selecting for pigs that more rapidly become non-shedders. In this case, RNAseq analysis of whole blood samples from persistent and low-shedding animals identified genes whose expression level was associated with variation in shedding (Kommadath et al, 2014). Furthermore, when blood taken from the same animals prior to infection was analyzed, this difference in gene expression was also present.…”