In silico analysis of autoimmune diseases and genetic relationships to vaccination against infectious diseases.
In silico analysis of autoimmune diseases and genetic relationships to vaccination against infectious diseases.
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DOI：
10.1186/s12865-014-0061-0
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发表时间：
2014-12-09
期刊：
影响因子：
3
通讯作者：
Madhavan S
中科院分区：
文献类型：
--
作者：
McGarvey PB;Suzek BE;Baraniuk JN;Rao S;Conkright B;Lababidi S;Sutherland A;Forshee R;Madhavan S
几乎普遍的疫苗接种要求对疫苗安全性进行严格的药物警戒，并严格限制对不良事件的耐受性。鉴于疫苗接种率高、自身免疫的背景发病率低、疫苗接种后发生自身免疫性疾病（AID）的时间可变，评估疫苗接种后发生自身免疫性疾病（AID）的报告具有挑战性。为了确定疫苗相关AID不良自身免疫事件的生物学合理途径，我们使用系统生物学方法创建了一个在特定疾病中活跃的先天性和适应性免疫机制矩阵，对疫苗抗原，佐剂，防腐剂和稳定剂的反应，用于疫苗不良事件报告系统中发现的最常见的疫苗相关AID。本报告重点介绍格林-巴利综合征（GBS）、风湿性关节炎（RA）、系统性红斑狼疮（SLE）和特发性（或免疫性）血小板减少性紫癜（ITP）。多个策划的数据库和PubMed文献的自动文本挖掘确定了667个与RA相关的基因，448个与SLE相关，49个与ITP相关，73个与GBS相关。虽然所有数据源都提供了有价值和独特的基因关联，但使用自然语言处理（NLP）算法的文本挖掘提供了最多的信息，但需要进行管理以删除不正确的关联。六个基因与所有四种艾滋病相关。这四种艾滋病共有33条通路。将基因分为12个免疫系统相关类别，发现RA中的“Th 17 T细胞亚型”基因多于其他AIDS，与RA相关的“趋化因子+受体”基因多于SLE。将基因网络可视化并聚类成具有每个AID的特定基因簇的互连模块，包括具有10个C-X-C基序趋化因子的RA中的一个。与GBS、GBS肽自身抗原、甲型流感感染和流感疫苗接种相关的基因的交叉产生了一个基因子网络，该基因子网络推断了MAPK信号通路在流感疫苗相关GBS中的可能作用。结果显示，独特的和共同的基因集，途径，免疫系统类别和功能簇的基因在四个自身免疫性疾病表明，它是可能的发展自身免疫性和炎症事件的分子分类。将这些信息与细胞和其他疾病反应相结合，将大大有助于评估接种疫苗后潜在的免疫介导的不良事件。本文的在线版本（doi：10.1186/s12865-014-0061-0）包含补充材料，可供授权用户使用。
Near universal administration of vaccines mandates intense pharmacovigilance for vaccine safety and a stringently low tolerance for adverse events. Reports of autoimmune diseases (AID) following vaccination have been challenging to evaluate given the high rates of vaccination, background incidence of autoimmunity, and low incidence and variable times for onset of AID after vaccinations. In order to identify biologically plausible pathways to adverse autoimmune events of vaccine-related AID, we used a systems biology approach to create a matrix of innate and adaptive immune mechanisms active in specific diseases, responses to vaccine antigens, adjuvants, preservatives and stabilizers, for the most common vaccine-associated AID found in the Vaccine Adverse Event Reporting System. This report focuses on Guillain-Barre Syndrome (GBS), Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Idiopathic (or immune) Thrombocytopenic Purpura (ITP). Multiple curated databases and automated text mining of PubMed literature identified 667 genes associated with RA, 448 with SLE, 49 with ITP and 73 with GBS. While all data sources provided valuable and unique gene associations, text mining using natural language processing (NLP) algorithms provided the most information but required curation to remove incorrect associations. Six genes were associated with all four AIDs. Thirty-three pathways were shared by the four AIDs. Classification of genes into twelve immune system related categories identified more “Th17 T-cell subtype” genes in RA than the other AIDs, and more “Chemokine plus Receptors” genes associated with RA than SLE. Gene networks were visualized and clustered into interconnected modules with specific gene clusters for each AID, including one in RA with ten C-X-C motif chemokines. The intersection of genes associated with GBS, GBS peptide auto-antigens, influenza A infection, and influenza vaccination created a subnetwork of genes that inferred a possible role for the MAPK signaling pathway in influenza vaccine related GBS. Results showing unique and common gene sets, pathways, immune system categories and functional clusters of genes in four autoimmune diseases suggest it is possible to develop molecular classifications of autoimmune and inflammatory events. Combining this information with cellular and other disease responses should greatly aid in the assessment of potential immune-mediated adverse events following vaccination. The online version of this article (doi:10.1186/s12865-014-0061-0) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Chang KH;Chuang TJ;Lyu RK;Ro LS;Wu YR;Chang HS;Huang CC;Kuo HC;Hsu WC;Chu CC;Chen CM
通讯作者：
Chen CM
DOI：
10.1073/pnas.93.23.12969
发表时间：
1996-11-12
影响因子：
11.1
作者：
Arany, Z;Huang, LE;Livingston, DM
通讯作者：
Livingston, DM
影响因子：
4.2
作者：
Brown, EG;Wood, L;Wood, S
通讯作者：
Wood, S
影响因子：
3.7
作者：
Bauer-Mehren A;Bundschus M;Rautschka M;Mayer MA;Sanz F;Furlong LI
通讯作者：
Furlong LI
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y