Show simple item record

dc.contributor.authorHall, Thomas J.
dc.contributor.authorMullen, Michael P.
dc.contributor.authorMcHugo, Gillian
dc.contributor.authorKillick, Kate E.
dc.contributor.authorRing, Siobhán C.
dc.contributor.authorBerry, Donagh P.
dc.contributor.authorCorreia, Carolina N.
dc.contributor.authorBrowne, John A.
dc.contributor.authorGordon, Stephen V.
dc.contributor.authorMacHugh, David E.
dc.identifier.citationHall, T. J. et al (2021). Integrative genomics of the mammalian alveolar macrophage response to intraceullular mycobacteria. BMC Genomics. 22: 343.
dc.description.abstractBovine TB (bTB), caused by infection with Mycobacterium bovis, is a major endemic disease affecting global cattle production. The key innate immune cell that first encounters the pathogen is the alveolar macrophage, previously shown to be substantially reprogrammed during intracellular infection by the pathogen. Here we use differential expression, and correlation- and interaction-based network approaches to analyse the host response to infection with M. bovis at the transcriptome level to identify core infection response pathways and gene modules. These outputs were then integrated with genome-wide association study (GWAS) data sets to enhance detection of genomic variants for susceptibility/resistance to M. bovis infection. Results: The host gene expression data consisted of RNA-seq data from bovine alveolar macrophages (bAM) infected with M. bovis at 24 and 48 h post-infection (hpi) compared to non-infected control bAM. These RNA-seq data were analysed using three distinct computational pipelines to produce six separate gene sets: 1) DE genes filtered using stringent fold-change and P-value thresholds (DEG-24: 378 genes, DEG-48: 390 genes); 2) genes obtained from expression correlation networks (CON-24: 460 genes, CON-48: 416 genes); and 3) genes obtained from differential expression networks (DEN-24: 339 genes, DEN-48: 495 genes). These six gene sets were integrated with three bTB breed GWAS data sets by employing a new genomics data integration tool—gwinteR. Using GWAS summary statistics, this methodology enabled detection of 36, 102 and 921 prioritised SNPs for Charolais, Limousin and Holstein-Friesian, respectively. Conclusions: The results from the three parallel analyses showed that the three computational approaches could identify genes significantly enriched for SNPs associated with susceptibility/resistance to M. bovis infection. Results indicate distinct and significant overlap in SNP discovery, demonstrating that network-based integration of biologically relevant transcriptomics data can leverage substantial additional information from GWAS data sets. These analyses also demonstrated significant differences among breeds, with the Holstein-Friesian breed GWAS proving most useful for prioritising SNPS through data integration. Because the functional genomics data were generated using bAM from this population, this suggests that the genomic architecture of bTB resilience traits may be more breed-specific than previously assumed.en_US
dc.relation.ispartofBMC Genomicsen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.subjectAlveolar macrophageen_US
dc.subjectIntegrative genomicsen_US
dc.subjectMycobacterium bovisen_US
dc.titleIntegrative genomics of the mammalian alveolar macrophage response to intraceullular mycobacteriaen_US
dc.contributor.affiliationAthlone Institute of Technologyen_US
dc.contributor.sponsorThis study was supported by Science Foundation Ireland (SFI) Investigator Programme Awards to D.E.M. and S.V.G. (grant nos. SFI/08/IN.1/B2038 and SFI/15/IA/3154); a Department of Agriculture, Food and the Marine (DAFM) project award to D.E.M (TARGET-TB; grant no. 17/RD/US-ROI/52); and a European Union Framework 7 project grant to D.E.M. (no: KBBE-211602- MACROSYS).en_US
dc.subject.departmentBioscience Research Institute AITen_US

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International