title: COMPASS identifies T-cell subsets correlated with clinical outcomes.
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.
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Finak
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ushey
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
authors.forename: Chetan
authors.initials: C
authors.lastname: Seshadri
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hawn
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Nicole
authors.identifier: 0000000312983676
authors.initials: N
authors.lastname: Frahm
authors.affiliation: 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.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.affiliation: 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.
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
authors.affiliation: 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.
authors.forename: Willem
authors.initials: W
authors.lastname: Hanekom
authors.affiliation: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Bart
authors.affiliation: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.affiliation: Data Management Unit, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, Thailand.
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.affiliation: Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Ratchathewi, Bangkok, Thailand.
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.affiliation: Vaccine Trials Center, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, Thailand.
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: US Army Military HIV Research Program, Walter Reed Army Institute of Research; Henry M. Jackson Foundation, Bethesda, Maryland, USA.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Ratchathewi, Bangkok, Thailand.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.affiliation: US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Ratchathewi, Bangkok, Thailand.
authors.forename: Nicos
authors.initials: N
authors.lastname: Karasavvas
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Gilbert
authors.affiliation: 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.
authors.forename: Stephen
authors.initials: S
authors.lastname: C De Rosa
authors.affiliation: 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.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Gottardo
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015686:Gene Products, env / Q000276:immunology / Q000627:therapeutic use; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D064368:Healthy Volunteers; D006801:Humans; D007111:Immunity, Cellular; D007070:Immunoglobulin A / Q000097:blood; D008297:Male; D059010:Single-Cell Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015686:Gene Products, env; D007070:Immunoglobulin A