Applications of Systems Biology to Improve Pig Health

  • Martine Schroyen
  • Haibo Liu
  • Christopher K. TuggleEmail author


In the pig, there are thus far only a handful of examples of health/disease studies approaching a systems biology level analysis, and this is in sharp contrast to the substantial amount of published porcine data on whole genome, transcriptome and proteome experiments with regard to economically important swine diseases. However, systems biology is very powerful since it attempts to understand how these distinct -ome parts work together to create emergent properties that are less likely to be recognized in the analysis of only one component of the system. By integration of the different -omics datasets, systems biology tries to create a more complete understanding of the observed immune response. Until now, such integrative analyses are still in their infancy in terms of application to pig health.

In this chapter, we will cover systems biology tools for network analyses and multilevel data integration, and give examples of their implementation in pig disease studies. Next, we will discuss the need for visualization to interpret the vast amount of data created in -omics studies. Furthermore, the upcoming use of bloodomics is described, since blood is a very relevant immune-related tissue and biomarkers in the blood can easily be assessed and implemented in selection strategies. We conclude with specific examples of -omics and initial systems biology methods on viral (PRRSv) and bacterial (Salmonella) infections, since both agents are economically important pathogens causing disease in pigs and substantial genomics analyses on the response to these pathogens have been conducted to date. In the future, forthcoming consortia such as the FAANG project will accelerate our ability to apply systems biology tools to improving pig health.


Quantitative Trait Locus Swine Leukocyte Antigen Bronchial Lymph Node Weight Gain Group PRRSv Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abbas AR, Baldwin D, Ma Y, Ouyang W, Gurney A, Martin F, Fong S, van Lookeren Campagne M, Godowski P, Williams PM, Chan AC, Clark HF (2005) Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data. Genes Immun 6:319–331PubMedCrossRefGoogle Scholar
  2. Ait-Ali T, Wilson AD, Carre W, Westcott DG, Frossard JP, Mellencamp MA, Mouzaki D, Matika O, Waddington D, Drew TW, Bishop SC, Archibald AL (2011) Host inhibits replication of European porcine reproductive and respiratory syndrome virus in macrophages by altering differential regulation of type-I interferon transcriptional response. Immunogenetics 63:437–448PubMedCrossRefGoogle Scholar
  3. Arakawa A, Okumura N, Taniguchi M, Hayashi T, Hirose K, Fukawa K, Ito T, Matsumoto T, Uenishi H, Mikawa S (2015) Genome-wide association QTL mapping for teat number in a purebred population of Duroc pigs. Anim Genet 46(5):571–575PubMedCrossRefGoogle Scholar
  4. Archibald AL, Haley CS, Brown JF, Couperwhite S, McQueen HA, Nicholson D, Coppieters W, Van de Weghe A, Stratil A, Wintero AK et al (1995) The PiGMaP consortium linkage map of the pig (Sus scrofa). Mamm Genome 6:157–175PubMedCrossRefGoogle Scholar
  5. Badaoui B, Tuggle CK, Hu Z, Reecy JM, Ait-Ali T, Anselmo A, Botti S (2013) Pig immune response to general stimulus and to porcine reproductive and respiratory syndrome virus infection: a meta-analysis approach. BMC Genomics 14:220PubMedPubMedCentralCrossRefGoogle Scholar
  6. Badaoui B, Rutigliano T, Anselmo A, Vanhee M, Nauwynck H, Giuffra E, Botti S (2014) RNA-sequence analysis of primary alveolar macrophages after in vitro infection with porcine reproductive and respiratory syndrome virus strains of differing virulence. PLoS One 9, e91918PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bao H, Kommadath A, Plastow GS, Tuggle CK, le Guan L, Stothard P (2014) MicroRNA buffering and altered variance of gene expression in response to Salmonella infection. PLoS One 9, e94352PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bao H, Kommadath A, Liang G, Sun X, Arantes AS, Tuggle CK, Bearson SMD, Plastow GS, Stothard P, Guan LL (2015) Genome-Wide whole blood microRNAome and transcriptome analyses revealed miRNA-mRNA regulated host response to foodborne pathogen Salmonella infection in swine. Sci Rep 5:12620PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bates JS, Petry DB, Eudy J, Bough L, Johnson RK (2008) Differential expression in lung and bronchial lymph node of pigs with high and low responses to infection with porcine reproductive and respiratory syndrome virus. J Anim Sci 86:3279–3289PubMedCrossRefGoogle Scholar
  10. Bearson SM, Allen HK, Bearson BL, Looft T, Brunelle BW, Kich JD, Tuggle CK, Bayles DO, Alt D, Levine UY, Stanton TB (2013) Profiling the gastrointestinal microbiota in response to Salmonella: low versus high Salmonella shedding in the natural porcine host. Infect Genet Evol 16:330–340PubMedCrossRefGoogle Scholar
  11. Bebek G, Koyuturk M, Price ND, Chance MR (2012) Network biology methods integrating biological data for translational science. Brief Bioinform 13:446–459PubMedPubMedCentralCrossRefGoogle Scholar
  12. Benoist C, Lanier L, Merad M, Mathis D (2012) Consortium biology in immunology: the perspective from the Immunological Genome Project. Nat Rev Immunol 12:734–740PubMedCrossRefGoogle Scholar
  13. Boddicker N, Waide EH, Rowland RR, Lunney JK, Garrick DJ, Reecy JM, Dekkers JC (2012) Evidence for a major QTL associated with host response to porcine reproductive and respiratory syndrome virus challenge. J Anim Sci 90:1733–1746PubMedCrossRefGoogle Scholar
  14. Boddicker NJ, Garrick DJ, Rowland RR, Lunney JK, Reecy JM, Dekkers JC (2013) Validation and further characterization of a major quantitative trait locus associated with host response to experimental infection with porcine reproductive and respiratory syndrome virus. Anim Genet 45:48–58PubMedCrossRefGoogle Scholar
  15. Boddicker NJ, Bjorkquist A, Rowland RR, Lunney JK, Reecy JM, Dekkers JC (2014) Genome-wide association and genomic prediction for host response to porcine reproductive and respiratory syndrome virus infection. Genet Sel Evol 46:18PubMedPubMedCentralCrossRefGoogle Scholar
  16. Callaway TR, Edrington TS, Anderson RC, Byrd JA, Nisbet DJ (2008) Gastrointestinal microbial ecology and the safety of our food supply as related to Salmonella. J Anim Sci 86:E163–E172PubMedCrossRefGoogle Scholar
  17. Carbon S, Ireland A, Mungall CJ, Shu S, Marshall B, Lewis S (2009) AmiGO: online access to ontology and annotation data. Bioinformatics 25:288–289PubMedCrossRefGoogle Scholar
  18. Chaussabel D (2015) Assessment of immune status using blood transcriptomics and potential implications for global health. Semin Immunol 27:58–66PubMedCrossRefGoogle Scholar
  19. Chaussabel D, Pascual V, Banchereau J (2010) Assessing the human immune system through blood transcriptomics. BMC Biol 8:84PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chomwisarutkun K, Murani E, Brunner R, Ponsuksili S, Wimmers K (2013) QTL region-specific microarrays reveal differential expression of positional candidate genes of signaling pathways associated with the liability for the inverted teat defect. Anim Genet 44:139–148PubMedCrossRefGoogle Scholar
  21. Clapperton M, Diack AB, Matika O, Glass EJ, Gladney CD, Mellencamp MA, Hoste A, Bishop SC (2009) Traits associated with innate and adaptive immunity in pigs: heritability and associations with performance under different health status conditions. Genet Sel Evol 41:54PubMedPubMedCentralCrossRefGoogle Scholar
  22. Cong P, Xiao S, Chen Y, Wang L, Gao J, Li M, He Z, Guo Y, Zhao G, Zhang X, Chen L, Mo D, Liu X (2014) Integrated miRNA and mRNA transcriptomes of porcine alveolar macrophages (PAM cells) identifies strain-specific miRNA molecular signatures associated with H-PRRSV and N-PRRSV infection. Mol Biol Rep 41:5863–5875PubMedCrossRefGoogle Scholar
  23. Contreras J, Rao DS (2012) MicroRNAs in inflammation and immune responses. Leukemia 26:404–413PubMedCrossRefGoogle Scholar
  24. da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57CrossRefGoogle Scholar
  25. Dawson HD, Loveland JE, Pascal G, Gilbert JG, Uenishi H, Mann KM, Sang Y, Zhang J, Carvalho-Silva D, Hunt T, Hardy M, Hu Z, Zhao SH, Anselmo A, Shinkai H, Chen C, Badaoui B, Berman D, Amid C, Kay M, Lloyd D, Snow C, Morozumi T, Cheng RP, Bystrom M, Kapetanovic R, Schwartz JC, Kataria R, Astley M, Fritz E, Steward C, Thomas M, Wilming L, Toki D, Archibald AL, Bed’Hom B, Beraldi D, Huang TH, Ait-Ali T, Blecha F, Botti S, Freeman TC, Giuffra E, Hume DA, Lunney JK, Murtaugh MP, Reecy JM, Harrow JL, Rogel-Gaillard C, Tuggle CK (2013) Structural and functional annotation of the porcine immunome. BMC Genomics 14:332PubMedPubMedCentralCrossRefGoogle Scholar
  26. Doeschl-Wilson AB (2011) The role of mathematical models of host-pathogen interactions for livestock health and production – a review. Animal 5:895–910PubMedCrossRefGoogle Scholar
  27. Doeschl-Wilson A, Galina-Pantoja L (2010) Using Mathematical Models to Gain Insight into Host-Pathogen Interaction in Mammals: Porcine Reproductive and Respiratory Syndrome. In: Barton AW (ed) Host-Pathogen Interactions: Genetics, Immunology, Physiology. Nova Science Publishers Inc, New York, p 109–131Google Scholar
  28. Doeschl-Wilson AB, Bishop SC, Kyriazakis I, Villanueva B (2012) Novel methods for quantifying individual host response to infectious pathogens for genetic analyses. Front Genet 3:266PubMedPubMedCentralGoogle Scholar
  29. Dohner K, Sodeik B (2005) The role of the cytoskeleton during viral infection. Curr Top Microbiol Immunol 285:67–108PubMedGoogle Scholar
  30. Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z (2009) GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics 10:48PubMedPubMedCentralCrossRefGoogle Scholar
  31. Edwards RA, Olsen GJ, Maloy SR (2002) Comparative genomics of closely related salmonellae. Trends Microbiol 10:94–99PubMedCrossRefGoogle Scholar
  32. ENCODE Project Consortium (2011) A user’s guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol 9, e1001046CrossRefGoogle Scholar
  33. Endale Ahanda ML, Fritz ER, Estelle J, Hu ZL, Madsen O, Groenen MA, Beraldi D, Kapetanovic R, Hume DA, Rowland RR, Lunney JK, Rogel-Gaillard C, Reecy JM, Giuffra E (2012) Prediction of altered 3’- UTR miRNA-binding sites from RNA-Seq data: the swine leukocyte antigen complex (SLA) as a model region. PLoS One 7, e48607PubMedPubMedCentralCrossRefGoogle Scholar
  34. Ernst CW, Steibel JP (2013) Molecular advances in QTL discovery and application in pig breeding. Trends Genet 29:215–224PubMedCrossRefGoogle Scholar
  35. Flori L, Gao Y, Laloe D, Lemonnier G, Leplat JJ, Teillaud A, Cossalter AM, Laffitte J, Pinton P, de Vaureix C, Bouffaud M, Mercat MJ, Lefevre F, Oswald IP, Bidanel JP, Rogel-Gaillard C (2011) Immunity traits in pigs: substantial genetic variation and limited covariation. PLoS One 6, e22717PubMedPubMedCentralCrossRefGoogle Scholar
  36. Foley SL, Lynne AM, Nayak R (2008) Salmonella challenges: prevalence in swine and poultry and potential pathogenicity of such isolates. J Anim Sci 86:E149–E162PubMedCrossRefGoogle Scholar
  37. Fowler KE, Pong-Wong R, Bauer J, Clemente EJ, Reitter CP, Affara NA, Waite S, Walling GA, Griffin DK (2013) Genome wide analysis reveals single nucleotide polymorphisms associated with fatness and putative novel copy number variants in three pig breeds. BMC Genomics 14:784PubMedPubMedCentralCrossRefGoogle Scholar
  38. Freeman TC, Goldovsky L, Brosch M, van Dongen S, Maziere P, Grocock RJ, Freilich S, Thornton J, Enright AJ (2007) Construction, visualisation, and clustering of transcription networks from microarray expression data. PLoS Comput Biol 3:2032–2042PubMedCrossRefGoogle Scholar
  39. Freeman TC, Ivens A, Baillie JK, Beraldi D, Barnett MW, Dorward D, Downing A, Fairbairn L, Kapetanovic R, Raza S, Tomoiu A, Alberio R, Wu C, Su AI, Summers KM, Tuggle CK, Archibald AL, Hume DA (2012) A gene expression atlas of the domestic pig. BMC Biol 10:90PubMedPubMedCentralCrossRefGoogle Scholar
  40. Galina-Pantoja L, Torremorell M, Deeb N, geiger B, Gladney C, Mellencamp MA (2006) DNA markers associated with reproductive traits during PRRSv infection. In: Proceedings of the 19th IVIS IPVS Congress DenmarkGoogle Scholar
  41. Genini S, Delputte PL, Malinverni R, Cecere M, Stella A, Nauwynck HJ, Giuffra E (2008) Genome-wide transcriptional response of primary alveolar macrophages following infection with porcine reproductive and respiratory syndrome virus. J Gen Virol 89:2550–2564PubMedPubMedCentralCrossRefGoogle Scholar
  42. Genini S, Paternoster T, Costa A, Botti S, Luini MV, Caprera A, Giuffra E (2012) Identification of serum proteomic biomarkers for early porcine reproductive and respiratory syndrome (PRRS) infection. Proc Natl Acad Sci U S A 10:48Google Scholar
  43. Haley CA, Dargatz DA, Bush EJ, Erdman MM, Fedorka-Cray PJ (2012) Salmonella prevalence and antimicrobial susceptibility from the National Animal Health Monitoring System Swine 2000 and 2006 studies. J Food Prot 75:428–436PubMedCrossRefGoogle Scholar
  44. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ (2008) Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther 27:104–119PubMedCrossRefGoogle Scholar
  45. Hicks J, Yoo D, Liu HC (2013) Characterization of the microRNAome in porcine reproductive and respiratory syndrome virus infected macrophages. PLoS One 8, e82054CrossRefGoogle Scholar
  46. Hollung K, Timperio AM, Olivan M, Kemp C, Coto-Montes A, Sierra V, Zolla L (2014) Systems biology: a new tool for farm animal science. Curr Protein Pept Sci 15:100–117PubMedCrossRefGoogle Scholar
  47. Holtkamp DJ, Kliebenstein JB, Neumann EJ, Zimmerman JJ, Rotto HF, Yoder TK, Wang C, Yeske PE, Mowrer CL, Haley CA (2013) Assessment of the economic impact of porcine reproductive and respiratory syndrome virus on United States pork producers. J Swine Health Prod 21:72–84Google Scholar
  48. Huang TH, Uthe JJ, Bearson SM, Demirkale CY, Nettleton D, Knetter S, Christian C, Ramer-Tait AE, Wannemuehler MJ, Tuggle CK (2011) Distinct peripheral blood RNA responses to Salmonella in pigs differing in Salmonella shedding levels: intersection of IFNG, TLR and miRNA pathways. PLoS One 6, e28768PubMedPubMedCentralCrossRefGoogle Scholar
  49. Hulst M, Loeffen W, Weesendorp E (2013) Pathway analysis in blood cells of pigs infected with classical swine fever virus: comparison of pigs that develop a chronic form of infection or recover. Arch Virol 158:325–339PubMedCrossRefGoogle Scholar
  50. Islam ZU, Bishop SC, Savill NJ, Rowland RR, Lunney JK, Trible B, Doeschl-Wilson AB (2013) Quantitative analysis of porcine reproductive and respiratory syndrome (PRRS) viremia profiles from experimental infection: a statistical modelling approach. PLoS One 8, e83567PubMedPubMedCentralCrossRefGoogle Scholar
  51. Jegou M, Gondret F, Vincent A, Trefeu C, Gilbert H, Louveau I (2016) Whole blood transcriptomics is relevant to identify molecular changes in response to genetic selection for feed efficiency and nutritional status in the pig. PLoS One 11, e0146550PubMedPubMedCentralCrossRefGoogle Scholar
  52. Jia X, Bi Y, Li J, Xie Q, Yang H, Liu W (2015) Cellular microRNA miR-26a suppresses replication of porcine reproductive and respiratory syndrome virus by activating innate antiviral immunity. Sci Rep 5:10651PubMedPubMedCentralCrossRefGoogle Scholar
  53. Kadarmideen HN, Watson-Haigh NS (2012) Building gene co-expression networks using transcriptomics data for systems biology investigations: Comparison of methods using microarray data. Bioinformation 8:855–861PubMedPubMedCentralCrossRefGoogle Scholar
  54. Kanehisa M, Goto S, Sato Y, Kawashima M, Furumichi M, Tanabe M (2014) Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res 42:D199–D205PubMedCrossRefGoogle Scholar
  55. Kapetanovic R, Fairbairn L, Downing A, Beraldi D, Sester DP, Freeman TC, Tuggle CK, Archibald AL, Hume DA (2013) The impact of breed and tissue compartment on the response of pig macrophages to lipopolysaccharide. BMC Genomics 14:581PubMedPubMedCentralCrossRefGoogle Scholar
  56. Kidd BA, Peters LA, Schadt EE, Dudley JT (2014) Unifying immunology with informatics and multiscale biology. Nat Immunol 15:118–127PubMedPubMedCentralCrossRefGoogle Scholar
  57. Kim HB, Isaacson RE (2015) The pig gut microbial diversity: understanding the pig gut microbial ecology through the next generation high throughput sequencing. Vet Microbiol 177:242–251PubMedCrossRefGoogle Scholar
  58. Knetter SM, Bearson SM, Huang TH, Kurkiewicz D, Schroyen M, Nettleton D, Berman D, Cohen V, Lunney JK, Ramer-Tait AE, Wannemuehler MJ, Tuggle CK (2015) Salmonella enterica serovar Typhimurium-infected pigs with different shedding levels exhibit distinct clinical, peripheral cytokine and transcriptomic immune response phenotypes. Innate Immun 21:227–241PubMedCrossRefGoogle Scholar
  59. Koesterke L, Milfeld K, Vaughn M, Stanzione D, Koltes J, Weeks N, Reecy J (2013) Optimizing the PCIT algorithm on stampede’s Xeon and Xeon Phi processors for faster discovery of biological networks. In: Proceedings of the conference on extreme science and engineering discovery environment: gateway to discoveryGoogle Scholar
  60. Koesterke L, Koltes J, Weeks N, Milfeld K, Vaughn M, Reecy J, Stanzione D (2014) Discovery of biological networks using an optimized partial correlation coefficient with information theory algorthim on Stampede’s Xeon and Xeons Phi processors. Concurrency Comput Pract Exp 26:2178–2190CrossRefGoogle Scholar
  61. Kogelman LJ, Cirera S, Zhernakova DV, Fredholm M, Franke L, Kadarmideen HN (2014) Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model. BMC Med Genomics 7:57PubMedPubMedCentralCrossRefGoogle Scholar
  62. Koltes JE, Fritz-Waters E, Eisley CJ, Choi I, Bao H, Kommadath A, Serao NV, Boddicker NJ, Abrams SM, Schroyen M, Loyd H, Tuggle CK, Plastow GS, Guan L, Stothard P, Lunney JK, Liu P, Carpenter S, Rowland RR, Dekkers JC, Reecy JM (2015) Identification of a putative quantitative trait nucleotide in guanylate binding protein 5 for host response to PRRS virus infection. BMC Genomics 16:412PubMedPubMedCentralCrossRefGoogle Scholar
  63. Kommadath A, Bao H, Arantes AS, Plastow GS, Tuggle CK, Bearson SM, le Guan L, Stothard P (2014) Gene co-expression network analysis identifies porcine genes associated with variation in Salmonella shedding. BMC Genomics 15:452PubMedPubMedCentralCrossRefGoogle Scholar
  64. Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9:559PubMedPubMedCentralCrossRefGoogle Scholar
  65. Li J, Chen Z, Zhao J, Fang L, Fang R, Xiao J, Chen X, Zhou A, Zhang Y, Ren L, Hu X, Zhao Y, Zhang S, Li N (2015a) Difference in microRNA expression and editing profile of lung tissues from different pig breeds related to immune responses to HP-PRRSV. Sci Rep 5:9549PubMedCrossRefGoogle Scholar
  66. Li L, Wei Z, Zhou Y, Gao F, Jiang Y, Yu L, Zheng H, Tong W, Yang S, Shan T, Liu F, Xia T, Tong G (2015b) Host miR-26a suppresses replication of porcine reproductive and respiratory syndrome virus by upregulating type I interferons. Virus Res 195:86–94PubMedCrossRefGoogle Scholar
  67. Lu Q, Bai J, Zhang L, Liu J, Jiang Z, Michal JJ, He Q, Jiang P (2012) Two-dimensional liquid chromatography-tandem mass spectrometry coupled with isobaric tags for relative and absolute quantification (iTRAQ) labeling approach revealed first proteome profiles of pulmonary alveolar macrophages infected with porcine reproductive and respiratory syndrome virus. J Proteome Res 11:2890–2903PubMedCrossRefGoogle Scholar
  68. Lunney JK, Ho CS, Wysocki M, Smith DM (2009) Molecular genetics of the swine major histocompatibility complex, the SLA complex. Dev Comp Immunol 33:362–374PubMedCrossRefGoogle Scholar
  69. Lunney JK, Steibel JP, Reecy JM, Fritz E, Rothschild MF, Kerrigan M, Trible B, Rowland RR (2011) Probing genetic control of swine responses to PRRSV infection: current progress of the PRRS host genetics consortium. BMC Proc 5(Suppl 4):S30PubMedPubMedCentralCrossRefGoogle Scholar
  70. Luo R, Fang L, Jin H, Wang D, An K, Xu N, Chen H, Xiao S (2014) Label-free quantitative phosphoproteomic analysis reveals differentially regulated proteins and pathway in PRRSV-infected pulmonary alveolar macrophages. J Proteome Res 13:1270–1280PubMedCrossRefGoogle Scholar
  71. Lynn DJ, Winsor GL, Chan C, Richard N, Laird MR, Barsky A, Gardy JL, Roche FM, Chan TH, Shah N, Lo R, Naseer M, Que J, Yau M, Acab M, Tulpan D, Whiteside MD, Chikatamarla A, Mah B, Munzner T, Hokamp K, Hancock RE, Brinkman FS (2008) InnateDB: facilitating systems-level analyses of the mammalian innate immune response. Mol Syst Biol 4:218PubMedPubMedCentralCrossRefGoogle Scholar
  72. Mach N, Gao Y, Lemonnier G, Lecardonnel J, Oswald IP, Estelle J, Rogel-Gaillard C (2013) The peripheral blood transcriptome reflects variations in immunity traits in swine: towards the identification of biomarkers. BMC Genomics 14:894PubMedPubMedCentralCrossRefGoogle Scholar
  73. McKnite AM, Bundy JW, Moural TW, Tart JK, Johnson TP, Jobman EE, Barnes SY, Qiu JK, Peterson DA, Harris SP, Rothschild MF, Galeota JA, Johnson RK, Kachman SD, Ciobanu DC (2014) Genomic analysis of the differential response to experimental infection with porcine circovirus 2b. Anim Genet 45:205–214PubMedCrossRefGoogle Scholar
  74. Mellencamp MA, Galina-Pantoja L, Gladney CD, Torremorell M (2008) Improving pig health through genomics: a view from the industry. Dev Biol (Basel) 132:35–41Google Scholar
  75. Mi H, Muruganujan A, Casagrande JT, Thomas PD (2013) Large-scale gene function analysis with the PANTHER classification system. Nat Protoc 8:1551–1566PubMedCrossRefGoogle Scholar
  76. Miller LC, Fleming D, Arbogast A, Bayles DO, Guo B, Lager KM, Henningson JN, Schlink SN, Yang HC, Faaberg KS, Kehrli ME Jr (2012) Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus. BMC Vet Res 8:208PubMedPubMedCentralCrossRefGoogle Scholar
  77. Mohr S, Liew CC (2007) The peripheral-blood transcriptome: new insights into disease and risk assessment. Trends Mol Med 13:422–432PubMedCrossRefGoogle Scholar
  78. Ni B, Wen LB, Wang R, Hao HP, Huan CC, Wang X, Huang L, Miao JF, Fan HJ, Mao X (2015) The involvement of FAK-PI3K-AKT-Rac1 pathway in porcine reproductive and respiratory syndrome virus entry. Biochem Biophys Res Commun 458(2):392–398PubMedCrossRefGoogle Scholar
  79. Ponsuksili S, Du Y, Murani E, Schwerin M, Wimmers K (2012) Elucidating molecular networks that either affect or respond to plasma cortisol concentration in target tissues of liver and muscle. Genetics 192:1109–1122PubMedPubMedCentralCrossRefGoogle Scholar
  80. Pop M, Walker AW, Paulson J, Lindsay B, Antonio M, Hossain MA, Oundo J, Tamboura B, Mai V, Astrovskaya I, Corrada Bravo H, Rance R, Stares M, Levine MM, Panchalingam S, Kotloff K, Ikumapayi UN, Ebruke C, Adeyemi M, Ahmed D, Ahmed F, Alam MT, Amin R, Siddiqui S, Ochieng JB, Ouma E, Juma J, Mailu E, Omore R, Morris JG, Breiman RF, Saha D, Parkhill J, Nataro JP, Stine OC (2014) Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition. Genome Biol 15:R76PubMedPubMedCentralCrossRefGoogle Scholar
  81. Rauw WM (2012) Immune response from a resource allocation perspective. Front Genet 3:267PubMedPubMedCentralCrossRefGoogle Scholar
  82. Reiner G, Dreher F, Drungowski M, Hoeltig D, Bertsch N, Selke M, Willems H, Gerlach GF, Probst I, Tuemmler B, Waldmann KH, Herwig R (2014) Pathway deregulation and expression QTLs in response to Actinobacillus pleuropneumoniae infection in swine. Mamm Genome 25:600–617PubMedCrossRefGoogle Scholar
  83. Reverter A, Chan EK (2008) Combining partial correlation and an information theory approach to the reversed engineering of gene co-expression networks. Bioinformatics 24:2491–2497PubMedCrossRefGoogle Scholar
  84. Reverter A, Hudson NJ, Nagaraj SH, Perez-Enciso M, Dalrymple BP (2010) Regulatory impact factors: unraveling the transcriptional regulation of complex traits from expression data. Bioinformatics 26:896–904PubMedCrossRefGoogle Scholar
  85. Rossow KD (1998) Porcine reproductive and respiratory syndrome. Vet Pathol 35:1–20PubMedCrossRefGoogle Scholar
  86. Sahadevan S, Gunawan A, Tholen E, Grosse-Brinkhaus C, Tesfaye D, Schellander K, Hofmann-Apitius M, Cinar MU, Uddin MJ (2014) Pathway based analysis of genes and interactions influencing porcine testis samples from boars with divergent androstenone content in back fat. PLoS One 9, e91077PubMedPubMedCentralCrossRefGoogle Scholar
  87. Sang Y, Brichalli W, Rowland RR, Blecha F (2014) Genome-wide analysis of antiviral signature genes in porcine macrophages at different activation statuses. PLoS One 9, e87613PubMedPubMedCentralCrossRefGoogle Scholar
  88. Schook LB, Beever JE, Rogers J, Humphray S, Archibald A, Chardon P, Milan D, Rohrer G, Eversole K (2005) Swine Genome Sequencing Consortium (SGSC): a strategic roadmap for sequencing the pig genome. Comp Funct Genomics 6:251–255PubMedPubMedCentralCrossRefGoogle Scholar
  89. Schroyen M, Tuggle CK (2015) Current transcriptomics in pig immunity research. Mamm Genome 26:1–20PubMedCrossRefGoogle Scholar
  90. Schroyen M, Steibel J, Koltes J, Choi I, Raney N, Eisley C, Fritz-Waters E, Reecy J, Dekkers J, Rowland R, Lunney J, Ernst C, Tuggle C (2015) Whole blood microarray analysis of pigs showing extreme phenotypes after a porcine reproductive and respiratory syndrome virus infection. BMC Genomics 16:516PubMedPubMedCentralCrossRefGoogle Scholar
  91. Schroyen M, Eisley C, Koltes JE, Fritz-Waters E, Choi I, Plastow GS, Guan L, Stothard P, Bao H, Kommadath A, Reecy JM, Lunney JK, Rowland RR, Dekkers JC, Tuggle CK (2016) Bioinformatic analyses in early host response to Porcine Reproductive and Respiratory Syndrome virus (PRRSV) reveals pathway differences between pigs with alternate genotypes for a major host response QTL. BMC Genomics 17:196PubMedPubMedCentralCrossRefGoogle Scholar
  92. Serão NV, Matika O, Kemp RA, Harding JC, Bishop SC, Plastow GS, Dekkers JC (2014) Genetic analysis of reproductive traits and antibody response in a PRRS outbreak herd. J Anim Sci 92:2905–2921PubMedCrossRefGoogle Scholar
  93. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504PubMedPubMedCentralCrossRefGoogle Scholar
  94. Sharma A, Lee JS, Dang CG, Sudrajad P, Kim HC, Yeon SH, Kang HS, Lee SH (2015) Stories and challenges of genome wide association studies in livestock – a review. Asian-Australas J Anim Sci 28:1371–1379PubMedPubMedCentralCrossRefGoogle Scholar
  95. Shen-Orr SS, Tibshirani R, Khatri P, Bodian DL, Staedtler F, Perry NM, Hastie T, Sarwal MM, Davis MM, Butte AJ (2010) Cell type-specific gene expression differences in complex tissues. Nat Methods 7:287–289PubMedPubMedCentralCrossRefGoogle Scholar
  96. Shoemaker JE, Lopes TJ, Ghosh S, Matsuoka Y, Kawaoka Y, Kitano H (2012) CTen: a web-based platform for identifying enriched cell types from heterogeneous microarray data. BMC Genomics 13:460PubMedPubMedCentralCrossRefGoogle Scholar
  97. Souza C, Choi I, Araujo K, Abrams S, Kerrigan M, Rowland RR, Lunney J (2013) Comparative serum immune responses of pigs after a challenge with porcine reproductive and respiratory syndrome virus (PRRSV). In: Proceedings of the 10th IVIS International Veterinary Immunology Symposium, P05.14 MilanGoogle Scholar
  98. Stear MJ, Bishop SC, Mallard BA, Raadsma H (2001) The sustainability, feasibility and desirability of breeding livestock for disease resistance. Res Vet Sci 71:1–7PubMedCrossRefGoogle Scholar
  99. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102:15545–15550PubMedPubMedCentralCrossRefGoogle Scholar
  100. Suchodolski JS, Markel ME, Garcia-Mazcorro JF, Unterer S, Heilmann RM, Dowd SE, Kachroo P, Ivanov I, Minamoto Y, Dillman EM, Steiner JM, Cook AK, Toresson L (2012) The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease. PLoS One 7, e51907PubMedPubMedCentralCrossRefGoogle Scholar
  101. Supek F, Bosnjak M, Skunca N, Smuc T (2011) REVIGO summarizes and visualizes long lists of gene ontology terms. PLoS One 6, e21800PubMedPubMedCentralCrossRefGoogle Scholar
  102. The FAANG Consortium, Andersson L, Archibald AL, Bottema CD, Brauning R, Burgess SC, Burt DW, Casas E, Cheng HH, Clarke L, Couldrey C, Dalrymple BP, Elsik CG, Foissac S, Giuffra E, Groenen MA, Hayes BJ, Huang LS, Khatib H, Kijas JW, Kim H, Lunney JK, McCarthy FM, McEwan JC, Moore S, Nanduri B, Notredame C, Palti Y, Plastow GS, Reecy JM, Rohrer GA, Sarropoulou E, Schmidt CJ, Silverstein J, Tellam RL, Tixier-Boichard M, Tosser-Klopp G, Tuggle CK, Vilkki J, White SN, Zhao S, Zhou H (2015) Coordinated international action to accelerate genome-to-phenome with FAANG, the Functional Annotation of Animal Genomes project. Genome Biol 16:57PubMedCentralCrossRefGoogle Scholar
  103. Tuggle CK, Towfic F, Honavar VG (2011) Introduction to Systems Biology for Animals Scientists. In: Te Pas MFW WH, Bannink A (eds) Systems biology and livestock science. Wiley-Blackwell, Oxford, pp 1–30CrossRefGoogle Scholar
  104. Uddin MJ, Cinar MU, Grosse-Brinkhaus C, Tesfaye D, Tholen E, Juengst H, Looft C, Wimmers K, Phatsara C, Schellander K (2011) Mapping quantitative trait loci for innate immune response in the pig. Int J Immunogenet 38:121–131PubMedCrossRefGoogle Scholar
  105. Uthe JJ, Wang Y, Qu L, Nettleton D, Tuggle CK, Bearson SM (2009) Correlating blood immune parameters and a CCT7 genetic variant with the shedding of Salmonella enterica serovar Typhimurium in swine. Vet Microbiol 135:384–388PubMedCrossRefGoogle Scholar
  106. Uthe JJ, Bearson SM, Qu L, Dekkers JC, Nettleton D, Rodriguez Torres Y, O’Connor AM, McKean JD, Tuggle CK (2011) Integrating comparative expression profiling data and association of SNPs with Salmonella shedding for improved food safety and porcine disease resistance. Anim Genet 42:521–534PubMedCrossRefGoogle Scholar
  107. Van Reeth K, Labarque G, Nauwynck H, Pensaert M (1999) Differential production of proinflammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity. Res Vet Sci 67:47–52PubMedCrossRefGoogle Scholar
  108. Videnska P, Sisak F, Havlickova H, Faldynova M, Rychlik I (2013) Influence of Salmonella enterica serovar Enteritidis infection on the composition of chicken cecal microbiota. BMC Vet Res 9:140PubMedPubMedCentralCrossRefGoogle Scholar
  109. Waide EH, Tuggle CK, Serão N, Schroyen M, Hess A, Rowland RRR, Lunney JK, Plastow G, Dekkers JCM (submitted) Genome wide association analysis of piglet response to infection with two porcine reproductive and respiratory syndrome virus isolates. J Anim Sci 87:1638–1647Google Scholar
  110. West CE, Ryden P, Lundin D, Engstrand L, Tulic MK, Prescott SL (2015) Gut microbiome and innate immune response patterns in IgE-associated eczema. Clin Exp Allergy 45:1419–1429PubMedCrossRefGoogle Scholar
  111. Wimmers K, Murani E, Schellander K, Ponsuksili S (2009) QTL for traits related to humoral immune response estimated from data of a porcine F2 resource population. Int J Immunogenet 36:141–151PubMedCrossRefGoogle Scholar
  112. Wysocki M, Chen H, Steibel JP, Kuhar D, Petry D, Bates J, Johnson R, Ernst CW, Lunney JK (2012) Identifying putative candidate genes and pathways involved in immune responses to porcine reproductive and respiratory syndrome virus (PRRSV) infection. Anim Genet 43:328–332PubMedCrossRefGoogle Scholar
  113. Xia J, Benner MJ, Hancock RE (2014) NetworkAnalyst--integrative approaches for protein-protein interaction network analysis and visual exploration. Nucleic Acids Res 42:W167–W174PubMedPubMedCentralCrossRefGoogle Scholar
  114. Xiao S, Wang Q, Jia J, Cong P, Mo D, Yu X, Qin L, Li A, Niu Y, Zhu K, Wang X, Liu X, Chen Y (2010) Proteome changes of lungs artificially infected with H-PRRSV and N-PRRSV by two-dimensional fluorescence difference gel electrophoresis. Virol J 7:107PubMedPubMedCentralCrossRefGoogle Scholar
  115. Xing J, Xing F, Zhang C, Zhang Y, Wang N, Li Y, Yang L, Jiang C, Wen C, Jiang Y (2014) Genome-wide gene expression profiles in lung tissues of pig breeds differing in resistance to porcine reproductive and respiratory syndrome virus. PLoS One 9, e86101PubMedPubMedCentralCrossRefGoogle Scholar
  116. Zhang H, Guo X, Ge X, Chen Y, Sun Q, Yang H (2009) Changes in the cellular proteins of pulmonary alveolar macrophage infected with porcine reproductive and respiratory syndrome virus by proteomics analysis. J Proteome Res 8:3091–3097PubMedCrossRefGoogle Scholar
  117. Zhou P, Zhai S, Zhou X, Lin P, Jiang T, Hu X, Jiang Y, Wu B, Zhang Q, Xu X, Li JP, Liu B (2011) Molecular characterization of transcriptome-wide interactions between highly pathogenic porcine reproductive and respiratory syndrome virus and porcine alveolar macrophages in vivo. Int J Biol Sci 7:947–959PubMedPubMedCentralCrossRefGoogle Scholar
  118. Zhu L, Yang S, Tong W, Zhu J, Yu H, Zhou Y, Morrison RB, Tong G (2013) Control of the PI3K/Akt pathway by porcine reproductive and respiratory syndrome virus. Arch Virol 158:1227–1234PubMedCrossRefGoogle Scholar
  119. Zimmerman J (2003) Historical Overview of PRRS virus. In: Zimmerman J, Yoon KJ, Neumann EJ (eds) 2003 PRRS compendium producer edition: a reference for pork producers. National Pork Board, Des Moines, pp 2–7Google Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Martine Schroyen
    • 1
  • Haibo Liu
    • 1
  • Christopher K. Tuggle
    • 1
    Email author
  1. 1.Department of Animal ScienceIowa State UniversityAmesUSA

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