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Nat Biotechnol. 2015 Jun;33(6):610-6. doi: 10.1038/nbt.3187. Epub 2015 May 25.

COMPASS identifies T-cell subsets correlated with clinical outcomes.

Author information

1
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
2
Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
3
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
4
Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
5
Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
6
Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
7
Data Management Unit, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, Thailand.
8
Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Ratchathewi, Bangkok, Thailand.
9
Vaccine Trials Center, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, Thailand.
10
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
11
US Army Military HIV Research Program, Walter Reed Army Institute of Research; Henry M. Jackson Foundation, Bethesda, Maryland, USA.
12
US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Ratchathewi, Bangkok, Thailand.
13
1] Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
14
1] Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA. [3] Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.

Abstract

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.

PMID:
26006008
PMCID:
PMC4569006
DOI:
10.1038/nbt.3187
[Indexed for MEDLINE]
Free PMC Article

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