COMPASS identifies T-cell subsets correlated with clinical outcomes.
COMPASS identifies T-cell subsets correlated with clinical outcomes.
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DOI：
10.1038/nbt.3187
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发表时间：
2015-06
影响因子：
46.9
通讯作者：
Gottardo R
中科院分区：
文献类型：
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作者：
Lin L;Finak G;Ushey K;Seshadri C;Hawn TR;Frahm N;Scriba TJ;Mahomed H;Hanekom W;Bart PA;Pantaleo G;Tomaras GD;Rerks-Ngarm S;Kaewkungwal J;Nitayaphan S;Pitisuttithum P;Michael NL;Kim JH;Robb ML;O'Connell RJ;Karasavvas N;Gilbert P;C De Rosa S;McElrath MJ;Gottardo R
流式细胞术和其他单细胞技术的进步使单个细胞的高维、高通量测量成为可能，并允许询问细胞群体的异质性。目前还缺乏充分利用这些技术的计算工具。在这里，我们介绍了COMPASS，一个用于抗原特异性T细胞亚群的无偏多功能分析的计算框架。Compass使用贝叶斯分层框架对所有观察到的功能细胞亚集进行建模，并选择最有可能表现出抗原特异性反应的细胞亚群。细胞子集的反应通过后验概率来量化，而受试者水平的反应通过两个新的总结统计来量化，这两个统计可以直接与临床结果相关，并描述个人(多)功能反应的质量。使用细胞因子产生的三个临床数据集，我们展示了COMPASS如何改进抗原特异性T细胞的特征，并揭示了RV144 HIV疫苗效力试验中被其他方法遗漏的新的细胞保护相关性。Compass以开源软件的形式提供。
Advances in flow cytometry and other single-cell technologies have enabled high-dimensional, high-throughput measurements of individual cells and allowed interrogation of cell population heterogeneity. Computational tools to take full advantage of these technologies are lacking. Here, we present COMPASS, a computational framework for unbiased polyfunctionality analysis of antigen-specific T-cell subsets. COMPASS uses a Bayesian hierarchical framework to model all observed functional cell subsets and select those most likely to exhibit antigen-specific responses. Cell-subset responses are quantified by posterior probabilities, while subject-level responses are quantified by two novel summary statistics that can be correlated directly with clinical outcome, and describe the quality of an individual’s (poly)functional response. Using three clinical datasets of cytokine production we demonstrate how COMPASS improves characterization of antigen-specific T cells and reveals novel cellular correlates of protection in the RV144 HIV vaccine efficacy trial that are missed by other methods. COMPASS is available as open-source software.