Structural and functional annotation of the porcine immunome.

Structural and functional annotation of the porcine immunome.
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猪免疫组的结构和功能注释。

DOI:
10.1186/1471-2164-14-332
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发表时间:
2013-05-15
期刊:
影响因子:
4.4
通讯作者:
Tuggle CK
Tuggle CK
中科院分区:
生物学2区
文献类型:
--
作者:
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

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家猪被认为是人类免疫学的优秀模型,这两个物种共享许多病原体。对传染病的易感性是猪生产性能的主要限制之一,但组成猪免疫组的基因的结构和功能还没有得到很好的表征。猪基因组的完成提供了注释猪免疫组以及比较和对比猪和人类免疫系统的机会。免疫应答注释组(IRAG)使用猪基因组组装10.2(Sscrofa10.2)的计算管理和手动注释,通过与其他物种中基因的基于序列的比较来完善目前可用的1,369个免疫相关基因的自动注释。在这些基因中,我们注释了3,472个转录本。注释提供了在几个免疫应答家族中基因扩增的证据,并确定了在凯萨林菌素和1型干扰素家族中偶蹄动物特异性扩增。我们发现了18个基因的基因重复,包括13个免疫反应基因和5个非免疫反应基因在注释过程中发现的。人工注释提供了许多新的可变剪接变异体和8个基因重复的证据。使用跨物种注释检测到超过1,100个没有猪序列证据的转录本。我们使用功能的方法来发现和准确注释猪免疫应答基因。来自血液、巨噬细胞或淋巴结的选定实验感染或免疫刺激的转录组数据的共表达聚类分析鉴定了在多种病原体或免疫刺激物感染后表现出相关阳性应答的大基因簇。有趣的是,该基因簇(簇4)富含已知的一般人类免疫应答基因,但含有许多未注释的猪基因。聚类4基因编码蛋白的系统发育分析表明,15%的基因表现出加速进化,而整个基因组中只有4.1%。这种广泛的注释极大地扩展了猪免疫组的主要部分的分子遗传学和结构的基于基因组的知识。我们在免疫应答期间使用共表达的互补功能方法为超过500个猪基因提供了新的推定免疫应答注释。我们对这一核心免疫组簇的系统发育分析证实了这组基因的快速进化变化,并且与其他物种一样,这些基因是猪在进化过程中适应病原体挑战的重要组成部分。这些全面和综合的分析增加了猪基因组序列的价值,并为猪免疫应答的全球分析和数据挖掘提供了重要工具。
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. 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. 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.
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发表时间: 2011-07
影响因子: 14.9
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期刊: BMC biology
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期刊: Science (New York, N.Y.)
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影响因子: 2.9
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