COMPASS identifies T-cell subsets correlated with clinical outcomes
Lin Lin1, Greg Finak1, Kevin Ushey1
1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Nature Biotechnology
|May 26, 2015
Summary
This study introduces COMPASS, a computational tool for analyzing T-cell responses. It identifies antigen-specific T-cell subsets and quantifies immune responses, aiding in vaccine development and clinical outcome correlation.
Area of Science:
- Immunology
- Computational Biology
- Bioinformatics
Background:
- Single-cell technologies generate high-dimensional data for cell heterogeneity analysis.
- Existing computational tools are insufficient for analyzing complex single-cell data.
- Understanding T-cell polyfunctionality is crucial for immune response assessment.
Purpose of the Study:
- To present COMPASS, a computational framework for unbiased combinatorial polyfunctionality analysis of antigen-specific T-cell subsets.
- To provide a tool for quantifying T-cell responses and identifying correlates of immunity.
- To enable better characterization of antigen-specific T cells in clinical studies.
Main Methods:
- Developed a Bayesian hierarchical framework for modeling cell subsets.
- Implemented COMPASS for unbiased analysis of combinatorial polyfunctionality.
- Utilized posterior probabilities to quantify cell-subset and subject-level responses.
Main Results:
- COMPASS successfully models observed cell subsets and identifies antigen-specific responses.
- Quantified T-cell responses using posterior probabilities and summary statistics.
- Revealed cellular correlates of protection missed by other methods in the RV144 HIV vaccine trial.
Conclusions:
- COMPASS offers an improved method for characterizing antigen-specific T cells.
- The framework aids in identifying cellular correlates of protection/immunity.
- COMPASS is available as open-source software for broader research application.
Related Concept Videos
T Cell Types and Functions
3.4K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.4K
T Cell Activation and Clonal Selection
17.8K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
17.8K
Cytotoxic T Cells-mediated Immune Response
8.4K
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
8.4K
Tumor Immunotherapy
2.5K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.5K


