COMPASS identifies T-cell subsets correlated with clinical outcomes

被引：223

作者：

Lin, Lin ^{[1
]}

Finak, Greg ^{[1
]}

Ushey, Kevin ^{[1
]}

Seshadri, Chetan ^{[2
]}

Hawn, Thomas R. ^{[2
]}

Frahm, Nicole ^{[1
]}

Scriba, Thomas J. ^{[3
]}

Mahomed, Hassan ^{[3
,4
]}

Hanekom, Willem ^{[3
,4
]}

Bart, Pierre-Alexandre ^{[5
]}

Pantaleo, Giuseppe ^{[5
]}

Tomaras, Georgia D. ^{[6
]}

Rerks-Ngarm, Supachai ^{[7
]}

Kaewkungwal, Jaranit ^{[8
]}

Nitayaphan, Sorachai ^{[9
]}

Pitisuttithum, Punnee ^{[10
]}

Michael, Nelson L. ^{[11
]}

Kim, Jerome H. ^{[11
]}

Robb, Merlin L. ^{[12
]}

O'Connell, Robert J. ^{[13
]}

Karasavvas, Nicos ^{[13
]}

Gilbert, Peter ^{[1
]}

De Rosa, Stephen C. ^{[1
,14
]}

McElrath, M. Juliana ^{[1
,2
,14
]}

Gottardo, Raphael ^{[1
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA

[2] Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA

[3] Univ Cape Town, Inst Infect Dis & Mol Med, South African TB Vaccine Initiat, ZA-7925 Cape Town, South Africa

[4] Univ Cape Town, Sch Child & Adolescent Hlth, ZA-7925 Cape Town, South Africa

[5] Univ Vaudois, Ctr Hosp, Lausanne, Switzerland

[6] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA

[7] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand

[8] Mahidol Univ, Fac Trop Med, Data Management Unit, Bangkok, Thailand

[9] Thai Component, Armed Forces Res Inst Med Sci, Bangkok, Thailand

[10] Mahidol Univ, Fac Trop Med, Vaccine Trials Ctr, Bangkok, Thailand

[11] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA

[12] Henry M Jackson Fdn, Walter Reed Army Inst Res, US Army Mil HIV Res Program, Bethesda, MD USA

[13] Armed Forces Res Inst Med Sci, US Army Med Component, Bangkok 10400, Thailand

[14] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA

来源：

NATURE BIOTECHNOLOGY | 2015年 / 33卷 / 06期

关键词：

FLOW-CYTOMETRY DATA; TUBERCULOSIS INFECTION; IMMUNE-RESPONSE; SOUTH-AFRICA; VACCINE; VIRUS; IMMUNIZATION; ASSAYS; TRIAL;

D O I：

10.1038/nbt.3187

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Advances in flow cytometry and other single-cell technologies have enabled high-dimensional, high-throughput measurements of individual cells as well as the interrogation of cell population heterogeneity. However, in many instances, computational tools to analyze the wealth of data generated by these technologies are lacking. Here, we present a computational framework for unbiased combinatorial polyfunctionality analysis of antigen-specific T-cell subsets (COMPASS). COMPASS uses a Bayesian hierarchical framework to model all observed cell subsets and select those most likely to have antigen-specific responses. Cell-subset responses are quantified by posterior probabilities, and human subject-level responses are quantified by two summary statistics that describe the quality of an individual's polyfunctional response and can be correlated directly with clinical outcome. Using three clinical data sets of cytokine production, we demonstrate how COMPASS improves characterization of antigen-specific T cells and reveals cellular 'correlates of protection/immunity' in the RV144 HIV vaccine efficacy trial that are missed by other methods. COMPASS is available as open-source software.

引用

页码：610 / +

页数：9

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