Structural and functional annotation of the porcine immunome

Harry D. Dawson; Jane E. Loveland; Géraldine Pascal; James G.R. Gilbert; Hirohide Uenishi; Katherine M. Mann; Yongming Sang; Jie Zhang; Denise Carvalho-Silva; Toby Hunt; Matthew Hardy; Zhiliang Hu; Shu Hong Zhao; Anna Anselmo; Hiroki Shinkai; Celine Chen; Bouabid Badaoui; Daniel Berman; Clara Amid; Mike Kay; David Lloyd; Catherine Snow; Takeya Morozumi; Ryan Pei Yen Cheng; Megan Bystrom; Ronan Kapetanovic; John C. Schwartz; Ranjit Kataria; Matthew Astley; Eric Fritz; Charles Steward; Mark Thomas; Laurens Wilming; Daisuke Toki; Alan L. Archibald; Bertrand Bed'Hom; Dario Beraldi; Ting Hua Huang; Tahar Ait-Ali; Frank Blecha; Sara Botti; Tom C. Freeman; Elisabetta Giuffra; David A. Hume; Joan K. Lunney; Michael P. Murtaugh; James M. Reecy; Jennifer L. Harrow; Claire Rogel-Gaillard; Christopher K. Tuggle

doi:10.1186/1471-2164-14-332

Structural and functional annotation of the porcine immunome

Harry D. Dawson, Jane E. Loveland, Géraldine Pascal, James G.R. Gilbert, Hirohide Uenishi, Katherine M. Mann, Yongming Sang, Jie Zhang, Denise Carvalho-Silva, Toby Hunt, Matthew Hardy, Zhiliang Hu, Shu Hong Zhao, Anna Anselmo, Hiroki Shinkai, Celine Chen, Bouabid Badaoui, Daniel Berman, Clara Amid, Mike KayDavid Lloyd, Catherine Snow, Takeya Morozumi, Ryan Pei Yen Cheng, Megan Bystrom, Ronan Kapetanovic, John C. Schwartz, Ranjit Kataria, Matthew Astley, Eric Fritz, Charles Steward, Mark Thomas, Laurens Wilming, Daisuke Toki, Alan L. Archibald, Bertrand Bed'Hom, Dario Beraldi, Ting Hua Huang, Tahar Ait-Ali, Frank Blecha, Sara Botti, Tom C. Freeman, Elisabetta Giuffra, David A. Hume, Joan K. Lunney, Michael P. Murtaugh, James M. Reecy, Jennifer L. Harrow, Claire Rogel-Gaillard, Christopher K. Tuggle

Veterinary and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

145 Scopus citations

Abstract

Background: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems.Results: The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome.Conclusions: This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig's adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response.

Original language	English (US)
Article number	332
Journal	BMC Genomics
Volume	14
Issue number	1
DOIs	https://doi.org/10.1186/1471-2164-14-332
State	Published - May 15 2013

Bibliographical note

Funding Information:
We thank Christelle Hennequet-Antier (INRA) for her advice and help for the q value computations and David Enard (Stanford University) for his advice and information on positive selection of whole genomes. We thank Danielle Goodband for her excellent technical support, and the COBRE core facilities in the Department of Anatomy and Physiology at Kansas State University (funded by NIH P20-RR017686) for technical and equipment support. We thank Yasaira Rodriguez Torres for help with Otterlace annotations. We acknowledge funding from the following sources: USDA-NRSP8 Bioinformatics Coordination (JMR, ZH, EF, CKT, JKL, RPYC, MB) USDA-NRSP8 Pig Genome Coordination funds (CKT, JKL, RPYC, MB) USDA-NRI-2009-35205-05192 and US-UK Fulbright Commission (CKT) INRA, Animal Genetics Department funds (CRG) USDA/ARS Project Plan # 1235-51000-055-00D (HDD) MAFF grant (Integrated research project for plant, insect and animal using genome technology, No. 1201) (HU) BBSRC grants (Ensembl): BB/E010520/1, BB/E010520/2, BB/I025328/1 and EC FP6 “Cutting edge genomics for sustainable animal breeding (SABRE)” (A. Archibald) USDA-NRI-2006-35204-17337, USDA AFRI NIFA/DHS 2010-39559-21860 and NIH P20-RR017686 (YS and FB) USDA ARS Project Plan #1245-32000-098 (JKL, KMM, DB) USDA ARS Beltsville Area Summer Undergraduate Fellowships (KMM, DB) BBSRC Grant BB/G004013/1 (RK) NSFC Outstanding Youth and 863 (2013AA102502) grant (31025026) (SHZ and JZ) US National Pork Board grant 10-139, USDA-NIFA PRRS CAP2 award 2008-55620-19132, and NIH T32 AI83196 fellowship (JCS and MPM) Wellcome Trust Grant 098051 (JEL, JLH, DCS, TH) MAFF Grant IRPPIAUGT-AG1201/2101 (HU, TM, HS, DT) Progetto AGER, grant no. 2011-0279, PoRRSCon project, grant no. 245141 (SB, BB, EG) 1USDA-ARS, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, MD 20705, USA. 2Informatics Department, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambs CB10 1SA, UK. 3INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380, Nouzilly, France. 4National Institute of Agrobiological Sciences, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan. 5USDA ARS BA Animal Parasitic Diseases Laboratory, Beltsville, MD 20705, USA. 6Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. 7Laboratory of Animal Genetics, Breeding, and Reproduction, Huazhong Agricultural University, Wuhan 430070, PR China. 8Department of Animal Science, Iowa State University, Ames, IA 50011, USA. 9Parco Tecnologico Padano, Integrative Biology Unit, via A. Einstein, 26900, Lodi, Italy. 10Institute of Japan Association for Technology in Agriculture, Forestry and Fisheries, 446-1 Ippaizuka, Kamiyokoba, Tsukuba, Ibaraki 305-0854, Japan. 11The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. 12Department of Veterinary and Biomedical Sciences, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA. 13National Bureau of Animal Genetic Resources, P.B. 129, GT Road By-Pass, Karnal 132001, (Haryana), India. 14INRA, UMR1313 Génétique Animale et Biologie Intégrative, F-78350, Jouy-en-Josas, France. 15Current affiliation: EMBL Outstation-Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambs CB10 1SD, UK.

Keywords

Accelerated evolution
Co-expression network
Genome annotation
Immune response
Phylogenetic analysis
Porcine

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Dawson, H. D., Loveland, J. E., Pascal, G., Gilbert, J. G. R., Uenishi, H., Mann, K. M., Sang, Y., Zhang, J., Carvalho-Silva, D., Hunt, T., Hardy, M., Hu, Z., Zhao, S. H., Anselmo, A., Shinkai, H., Chen, C., Badaoui, B., Berman, D., Amid, C., ... Tuggle, C. K. (2013). Structural and functional annotation of the porcine immunome. BMC Genomics, 14(1), Article 332. https://doi.org/10.1186/1471-2164-14-332

Dawson, HD, Loveland, JE, Pascal, G, Gilbert, JGR, 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, RPY, 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, vol. 14, no. 1, 332. https://doi.org/10.1186/1471-2164-14-332

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title = "Structural and functional annotation of the porcine immunome",

abstract = "Background: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems.Results: The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome.Conclusions: This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig's adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response.",

keywords = "Accelerated evolution, Co-expression network, Genome annotation, Immune response, Phylogenetic analysis, Porcine",

author = "Dawson, {Harry D.} and Loveland, {Jane E.} and G{\'e}raldine Pascal and Gilbert, {James G.R.} and Hirohide Uenishi and Mann, {Katherine M.} and Yongming Sang and Jie Zhang and Denise Carvalho-Silva and Toby Hunt and Matthew Hardy and Zhiliang Hu and Zhao, {Shu Hong} and Anna Anselmo and Hiroki Shinkai and Celine Chen and Bouabid Badaoui and Daniel Berman and Clara Amid and Mike Kay and David Lloyd and Catherine Snow and Takeya Morozumi and Cheng, {Ryan Pei Yen} and Megan Bystrom and Ronan Kapetanovic and Schwartz, {John C.} and Ranjit Kataria and Matthew Astley and Eric Fritz and Charles Steward and Mark Thomas and Laurens Wilming and Daisuke Toki and Archibald, {Alan L.} and Bertrand Bed'Hom and Dario Beraldi and Huang, {Ting Hua} and Tahar Ait-Ali and Frank Blecha and Sara Botti and Freeman, {Tom C.} and Elisabetta Giuffra and Hume, {David A.} and Lunney, {Joan K.} and Murtaugh, {Michael P.} and Reecy, {James M.} and Harrow, {Jennifer L.} and Claire Rogel-Gaillard and Tuggle, {Christopher K.}",

note = "Funding Information: We thank Christelle Hennequet-Antier (INRA) for her advice and help for the q value computations and David Enard (Stanford University) for his advice and information on positive selection of whole genomes. We thank Danielle Goodband for her excellent technical support, and the COBRE core facilities in the Department of Anatomy and Physiology at Kansas State University (funded by NIH P20-RR017686) for technical and equipment support. We thank Yasaira Rodriguez Torres for help with Otterlace annotations. We acknowledge funding from the following sources: USDA-NRSP8 Bioinformatics Coordination (JMR, ZH, EF, CKT, JKL, RPYC, MB) USDA-NRSP8 Pig Genome Coordination funds (CKT, JKL, RPYC, MB) USDA-NRI-2009-35205-05192 and US-UK Fulbright Commission (CKT) INRA, Animal Genetics Department funds (CRG) USDA/ARS Project Plan # 1235-51000-055-00D (HDD) MAFF grant (Integrated research project for plant, insect and animal using genome technology, No. 1201) (HU) BBSRC grants (Ensembl): BB/E010520/1, BB/E010520/2, BB/I025328/1 and EC FP6 “Cutting edge genomics for sustainable animal breeding (SABRE)” (A. Archibald) USDA-NRI-2006-35204-17337, USDA AFRI NIFA/DHS 2010-39559-21860 and NIH P20-RR017686 (YS and FB) USDA ARS Project Plan #1245-32000-098 (JKL, KMM, DB) USDA ARS Beltsville Area Summer Undergraduate Fellowships (KMM, DB) BBSRC Grant BB/G004013/1 (RK) NSFC Outstanding Youth and 863 (2013AA102502) grant (31025026) (SHZ and JZ) US National Pork Board grant 10-139, USDA-NIFA PRRS CAP2 award 2008-55620-19132, and NIH T32 AI83196 fellowship (JCS and MPM) Wellcome Trust Grant 098051 (JEL, JLH, DCS, TH) MAFF Grant IRPPIAUGT-AG1201/2101 (HU, TM, HS, DT) Progetto AGER, grant no. 2011-0279, PoRRSCon project, grant no. 245141 (SB, BB, EG) 1USDA-ARS, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, MD 20705, USA. 2Informatics Department, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambs CB10 1SA, UK. 3INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380, Nouzilly, France. 4National Institute of Agrobiological Sciences, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan. 5USDA ARS BA Animal Parasitic Diseases Laboratory, Beltsville, MD 20705, USA. 6Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. 7Laboratory of Animal Genetics, Breeding, and Reproduction, Huazhong Agricultural University, Wuhan 430070, PR China. 8Department of Animal Science, Iowa State University, Ames, IA 50011, USA. 9Parco Tecnologico Padano, Integrative Biology Unit, via A. Einstein, 26900, Lodi, Italy. 10Institute of Japan Association for Technology in Agriculture, Forestry and Fisheries, 446-1 Ippaizuka, Kamiyokoba, Tsukuba, Ibaraki 305-0854, Japan. 11The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. 12Department of Veterinary and Biomedical Sciences, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA. 13National Bureau of Animal Genetic Resources, P.B. 129, GT Road By-Pass, Karnal 132001, (Haryana), India. 14INRA, UMR1313 G{\'e}n{\'e}tique Animale et Biologie Int{\'e}grative, F-78350, Jouy-en-Josas, France. 15Current affiliation: EMBL Outstation-Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambs CB10 1SD, UK.",

year = "2013",

month = may,

day = "15",

doi = "10.1186/1471-2164-14-332",

language = "English (US)",

volume = "14",

journal = "BMC Genomics",

issn = "1471-2164",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Structural and functional annotation of the porcine immunome

AU - Dawson, Harry D.

AU - Loveland, Jane E.

AU - Pascal, Géraldine

AU - Gilbert, James G.R.

AU - Uenishi, Hirohide

AU - Mann, Katherine M.

AU - Sang, Yongming

AU - Zhang, Jie

AU - Carvalho-Silva, Denise

AU - Hunt, Toby

AU - Hardy, Matthew

AU - Hu, Zhiliang

AU - Zhao, Shu Hong

AU - Anselmo, Anna

AU - Shinkai, Hiroki

AU - Chen, Celine

AU - Badaoui, Bouabid

AU - Berman, Daniel

AU - Amid, Clara

AU - Kay, Mike

AU - Lloyd, David

AU - Snow, Catherine

AU - Morozumi, Takeya

AU - Cheng, Ryan Pei Yen

AU - Bystrom, Megan

AU - Kapetanovic, Ronan

AU - Schwartz, John C.

AU - Kataria, Ranjit

AU - Astley, Matthew

AU - Fritz, Eric

AU - Steward, Charles

AU - Thomas, Mark

AU - Wilming, Laurens

AU - Toki, Daisuke

AU - Archibald, Alan L.

AU - Bed'Hom, Bertrand

AU - Beraldi, Dario

AU - Huang, Ting Hua

AU - Ait-Ali, Tahar

AU - Blecha, Frank

AU - Botti, Sara

AU - Freeman, Tom C.

AU - Giuffra, Elisabetta

AU - Hume, David A.

AU - Lunney, Joan K.

AU - Murtaugh, Michael P.

AU - Reecy, James M.

AU - Harrow, Jennifer L.

AU - Rogel-Gaillard, Claire

AU - Tuggle, Christopher K.

N1 - Funding Information: We thank Christelle Hennequet-Antier (INRA) for her advice and help for the q value computations and David Enard (Stanford University) for his advice and information on positive selection of whole genomes. We thank Danielle Goodband for her excellent technical support, and the COBRE core facilities in the Department of Anatomy and Physiology at Kansas State University (funded by NIH P20-RR017686) for technical and equipment support. We thank Yasaira Rodriguez Torres for help with Otterlace annotations. We acknowledge funding from the following sources: USDA-NRSP8 Bioinformatics Coordination (JMR, ZH, EF, CKT, JKL, RPYC, MB) USDA-NRSP8 Pig Genome Coordination funds (CKT, JKL, RPYC, MB) USDA-NRI-2009-35205-05192 and US-UK Fulbright Commission (CKT) INRA, Animal Genetics Department funds (CRG) USDA/ARS Project Plan # 1235-51000-055-00D (HDD) MAFF grant (Integrated research project for plant, insect and animal using genome technology, No. 1201) (HU) BBSRC grants (Ensembl): BB/E010520/1, BB/E010520/2, BB/I025328/1 and EC FP6 “Cutting edge genomics for sustainable animal breeding (SABRE)” (A. Archibald) USDA-NRI-2006-35204-17337, USDA AFRI NIFA/DHS 2010-39559-21860 and NIH P20-RR017686 (YS and FB) USDA ARS Project Plan #1245-32000-098 (JKL, KMM, DB) USDA ARS Beltsville Area Summer Undergraduate Fellowships (KMM, DB) BBSRC Grant BB/G004013/1 (RK) NSFC Outstanding Youth and 863 (2013AA102502) grant (31025026) (SHZ and JZ) US National Pork Board grant 10-139, USDA-NIFA PRRS CAP2 award 2008-55620-19132, and NIH T32 AI83196 fellowship (JCS and MPM) Wellcome Trust Grant 098051 (JEL, JLH, DCS, TH) MAFF Grant IRPPIAUGT-AG1201/2101 (HU, TM, HS, DT) Progetto AGER, grant no. 2011-0279, PoRRSCon project, grant no. 245141 (SB, BB, EG) 1USDA-ARS, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, MD 20705, USA. 2Informatics Department, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambs CB10 1SA, UK. 3INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380, Nouzilly, France. 4National Institute of Agrobiological Sciences, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan. 5USDA ARS BA Animal Parasitic Diseases Laboratory, Beltsville, MD 20705, USA. 6Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. 7Laboratory of Animal Genetics, Breeding, and Reproduction, Huazhong Agricultural University, Wuhan 430070, PR China. 8Department of Animal Science, Iowa State University, Ames, IA 50011, USA. 9Parco Tecnologico Padano, Integrative Biology Unit, via A. Einstein, 26900, Lodi, Italy. 10Institute of Japan Association for Technology in Agriculture, Forestry and Fisheries, 446-1 Ippaizuka, Kamiyokoba, Tsukuba, Ibaraki 305-0854, Japan. 11The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. 12Department of Veterinary and Biomedical Sciences, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA. 13National Bureau of Animal Genetic Resources, P.B. 129, GT Road By-Pass, Karnal 132001, (Haryana), India. 14INRA, UMR1313 Génétique Animale et Biologie Intégrative, F-78350, Jouy-en-Josas, France. 15Current affiliation: EMBL Outstation-Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambs CB10 1SD, UK.

PY - 2013/5/15

Y1 - 2013/5/15

N2 - Background: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems.Results: The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome.Conclusions: This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig's adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response.

AB - Background: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems.Results: The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome.Conclusions: This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig's adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response.

KW - Accelerated evolution

KW - Co-expression network

KW - Genome annotation

KW - Immune response

KW - Phylogenetic analysis

KW - Porcine

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UR - http://www.scopus.com/inward/citedby.url?scp=84877935749&partnerID=8YFLogxK

U2 - 10.1186/1471-2164-14-332

DO - 10.1186/1471-2164-14-332

M3 - Article

C2 - 23676093

AN - SCOPUS:84877935749

SN - 1471-2164

VL - 14

JO - BMC Genomics

JF - BMC Genomics

IS - 1

M1 - 332

ER -

Structural and functional annotation of the porcine immunome

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