Experimental validation of the RATE tool for inferring HLA restrictions of T cell epitopes.
Experimental validation of the RATE tool for inferring HLA restrictions of T cell epitopes.
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DOI：
10.1186/s12865-017-0204-1
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发表时间：
2017-06-21
期刊：
影响因子：
3
通讯作者：
Sette A
中科院分区：
文献类型：
--
作者：
Paul S;Arlehamn CSL;Schulten V;Westernberg L;Sidney J;Peters B;Sette A
Rate工具是最近开发的，可以从HLA型受试者的免疫反应数据中计算出给定表位的HLA限制性，而不需要额外的繁琐实验。在这里，使用来自南非西开普省地区的191个结核病来源的表位和63名患有结核杆菌感染的健康个体的实验定义的限制数据来验证Rate。使用这个实验数据集，Rate工具用来推断限制的参数被优化，其中包括受试者对给定表位做出反应并表达给定等位基因的相对频率(Rf)，与一般测试群体相比，以及Fisher精确测试中相关的p值。我们还根据预测的表位与潜在的限制性HLA等位基因的结合亲和力，以及表达给定等位基因并对特定表位做出反应的个体的绝对数量，检查了进一步优化的可能性。不同的统计学指标，包括马修相关系数、准确度、敏感度和特异度，作为这些标准的函数被用来评估比率的表现。根据我们的结果，我们建议选择p值为 <； 0.01和RF为1.3的 ≥ 限制。通过推断由于缺乏必要的细胞系而无法通过实验确定限制的表位集以及与识别来自过敏患者的花粉来源的表位相关的额外数据集，证明了该工具的有效性。实验数据集被用来验证Rate工具，并优化了Rate工具用来推断约束的参数。使用优化的比率工具确定了新的人类白细胞抗原限制。本文的在线版本(doi：10.1186/s12865-0170204-1)包含补充材料，授权用户可以使用。
The RATE tool was recently developed to computationally infer the HLA restriction of given epitopes from immune response data of HLA typed subjects without additional cumbersome experimentation. Here, RATE was validated using experimentally defined restriction data from a set of 191 tuberculosis-derived epitopes and 63 healthy individuals with MTB infection from the Western Cape Region of South Africa. Using this experimental dataset, the parameters utilized by the RATE tool to infer restriction were optimized, which included relative frequency (RF) of the subjects responding to a given epitope and expressing a given allele as compared to the general test population and the associated p-value in a Fisher’s exact test. We also examined the potential for further optimization based on the predicted binding affinity of epitopes to potential restricting HLA alleles, and the absolute number of individuals expressing a given allele and responding to the specific epitope. Different statistical measures, including Matthew’s correlation coefficient, accuracy, sensitivity and specificity were used to evaluate performance of RATE as a function of these criteria. Based on our results we recommend selection of HLA restrictions with cutoffs of p-value < 0.01 and RF ≥ 1.3. The usefulness of the tool was demonstrated by inferring new HLA restrictions for epitope sets where restrictions could not be experimentally determined due to lack of necessary cell lines and for an additional data set related to recognition of pollen derived epitopes from allergic patients. Experimental data sets were used to validate RATE tool and the parameters used by the RATE tool to infer restriction were optimized. New HLA restrictions were identified using the optimized RATE tool. The online version of this article (doi:10.1186/s12865-017-0204-1) contains supplementary material, which is available to authorized users.