BIITE: A Tool to Determine HLA Class II Epitopes from T Cell ELISpot Data.
BIITE: A Tool to Determine HLA Class II Epitopes from T Cell ELISpot Data.
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DOI：
10.1371/journal.pcbi.1004796
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发表时间：
2016-03
影响因子：
4.3
通讯作者：
Asquith B
中科院分区：
文献类型：
--
作者：
Boelen L;O'Neill PK;Quigley KJ;Reynolds CJ;Maillere B;Robinson JH;Lertmemongkolchai G;Altmann DM;Boyton RJ;Asquith B
CD4+ T 细胞的激活需要识别由 HLA II 类分子呈递的肽，并且可以使用 ELISpot 测定进行实验评估。然而，即使给定个体的 HLA II 类基因型，识别哪种 II 类分子对给定肽产生阳性 ELISpot 反应也并非易事。两个主要困难是单个个体中可能形成的 HLA II 类分子的数量 (3-14) 以及 II 类分子缺乏明确的肽结合基序。在这里，我们提出了一个解释 ELISpot 数据的贝叶斯框架（BIITE：ELISpot 的贝叶斯免疫原性推理工具）；具体而言，BIITE 根据队列 ELISpot 数据识别哪些 HLA-II: 肽组合具有免疫原性。我们将 BIITE 应用于两个 ELISpot 数据集，并通过模拟探索预期性能。我们证明这种方法可以达到很高的准确度，具体取决于队列大小和队列内 ELISpot 测定的成功率。在研究宿主免疫反应时，一个中心问题是：“哪些肽引发 CD4+ T 细胞反应？” ELISpot 测定用于评估受试者是否对给定的肽有反应。然而，要确定由宿主 HLA 基因型编码的哪一种 HLA-II 分子负责该反应，需要进行额外的分析。我们提出了一种贝叶斯方法来解决这个问题，并已将其实现为与 BIITE 名称下的统计语言 R 一起使用。重要的是，BIITE 的目的是解释实验数据，而不是进行计算机预测。该方法同时考虑所有 HLA（在一组患者中）相对于给定肽的免疫原性，以处理 HLA 基因座基因之间的连锁不平衡。此外，用户可以以先验信息的形式输入他们可能拥有的附加信息（来自文献或其他实验）。该方法不仅适用于 HLA 基因，还可用于将正二元结果归因于任何多等位基因组。
Activation of CD4+ T cells requires the recognition of peptides that are presented by HLA class II molecules and can be assessed experimentally using the ELISpot assay. However, even given an individual’s HLA class II genotype, identifying which class II molecule is responsible for a positive ELISpot response to a given peptide is not trivial. The two main difficulties are the number of HLA class II molecules that can potentially be formed in a single individual (3–14) and the lack of clear peptide binding motifs for class II molecules. Here, we present a Bayesian framework to interpret ELISpot data (BIITE: Bayesian Immunogenicity Inference Tool for ELISpot); specifically BIITE identifies which HLA-II:peptide combination(s) are immunogenic based on cohort ELISpot data. We apply BIITE to two ELISpot datasets and explore the expected performance using simulations. We show this method can reach high accuracies, depending on the cohort size and the success rate of the ELISpot assay within the cohort. When studying the host immune response, a central question is: “which peptides elicit CD4+ T cell responses?” ELISpot assays are used to assess if subjects have responded to a given peptide. However, to determine which of the HLA-II molecules coded by the host HLA genotype is responsible for the reaction requires additional analysis. We present a Bayesian approach to solve this problem and have implemented it for use with the statistical language R under the BIITE moniker. Importantly, the aim of BIITE is to interpret experimental data, not to make in silico predictions. The method considers the immunogenicity of all HLA (in a cohort of patients) with respect to a given peptide simultaneously, in order to deal with linkage disequilibrium between genes of the HLA locus. Furthermore, users can enter additional information they might have (from literature or other experiments) in the form of prior information. The method is not exclusive to the HLA genes and can be used to attribute positive binary outcomes to any multi-allelic set of genes.