We propose to use a systems approach that combines well-defined cohorts with unbiased large-scale profiling to elucidate signatures defining immune responsiveness in the context of divergent disease outcomes. Standardization, both at the assay and analytical levels, will allow comparisons and integration of data across projects. To maximize the immune profiles of samples generated in our Projects?and the shared analysis and interpretation of data? we propose a Single Cell Phenotyping Core to conduct and analyze multiparameter immune markers using shared platforms. The platforms of the Core include mass cytometry (CyTOF) for multiparameter single cell analysis of samples from the Research Projects (Aim 1). This new technology, which overcomes many of the limitations of fluorescence-based flow cytometry, provides unprecedented cellular analysis of multiple cell populations simultaneously and is a powerful technique for translational investigations. Our core will support seamless web interface and in depth computational analysis needs of the projects (Aim 2). In addition, we will use nanowell-based single-cell analysis for multispectral imaging cytometry (MuSIC) to measure, analyze and report the surface expression of up to 16 markers on immunocytes in sorted populations of interest or in sparse samples, including synovial fluid and EM biopsies (Aim 3). Finally, we will extend the capabilities of the nanowell platform for performing single-cell RNA-sequencing, which provides a unique and unbiased approach for resolving heterogeneous subsets of immune cells (Aim 4). Array-wide RNA- sequencing of targeted cell types or sparse samples is an innovative platform to probe the intrinsic differences between cells of interest and to refine the molecular signatures of cells implicated in disease.
We propose to use a systems approach that combines well-defined cohorts with unbiased large-scale profiling to elucidate signatures defining immune responsiveness in the context of divergent disease outcomes. The goals of the Single Cell Immune Profiling Core are to provide data and high dimensional analysis for multiparameter analysis including CyTOF single-cell profiling, nanowell- based single-cell analysis, and single-cell RNA-Seq.
|Murray, Kristy O; Nolan, Melissa S; Ronca, Shannon E et al. (2018) The Neurocognitive and MRI Outcomes of West Nile Virus Infection: Preliminary Analysis Using an External Control Group. Front Neurol 9:111|
|Molony, Ryan D; Malawista, Anna; Montgomery, Ruth R (2018) Reduced dynamic range of antiviral innate immune responses in aging. Exp Gerontol 107:130-135|
|Martin-Gayo, Enrique; Cole, Michael B; Kolb, Kellie E et al. (2018) A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers. Genome Biol 19:10|
|Wang, Xiaomei; Malawista, Anna; Qian, Feng et al. (2018) Age-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes. Oncotarget 9:9572-9580|
|Cahill, Megan E; Conley, Samantha; DeWan, Andrew T et al. (2018) Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis. BMC Infect Dis 18:282|
|van Dijk, David; Sharma, Roshan; Nainys, Juozas et al. (2018) Recovering Gene Interactions from Single-Cell Data Using Data Diffusion. Cell 174:716-729.e27|
|Ordovas-Montanes, Jose; Dwyer, Daniel F; Nyquist, Sarah K et al. (2018) Allergic inflammatory memory in human respiratory epithelial progenitor cells. Nature 560:649-654|
|Mead, Benjamin E; Ordovas-Montanes, Jose; Braun, Alexandra P et al. (2018) Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types. BMC Biol 16:62|
|Avey, Stefan; Mohanty, Subhasis; Wilson, Jean et al. (2017) Multiple network-constrained regressions expand insights into influenza vaccination responses. Bioinformatics 33:i208-i216|
|Cahill, Megan E; Yao, Yi; Nock, David et al. (2017) West Nile Virus Seroprevalence, Connecticut, USA, 2000-2014. Emerg Infect Dis 23:708-710|
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