High-content flow cytometry and temporal data analysis for defining a cellular signature of graft-versus-host disease.

By Ryan Remy Brinkman, M. Gasparetto, Shang-Jung Lee, A. Ribickas, J. Perkins, W. Janssen, R. Smiley, Clay Smith. 2007

95 citations recorded by the source corpus.

Acute graft-versus-host disease (GVHD) is diagnosed by clinical and histologic criteria that are often nonspecific and typically apparent only after the disease is well established. Because GvHD is mediated by donor T cells and other immune effector cells, we sought to determine whether changes within a wide array of peripheral blood lymphocyte populations could predict the development of GvHD. Peripheral blood samples from 31 patients undergoing allogeneic blood and marrow transplant were analyzed for the proportion of 121 different subpopulations defined by 4-color combinations of lymphocyte phenotypic and activation markers at progressive time points posttransplant. Samples were processed using a newly developed high content flow cytometry technique and subjected to a spline- and functional linear discriminant analysis (FLDA)-based temporal analysis technique. This strategy identified a consistent posttransplant increase in the proportion and extent of fluctuation of CD3+CD4+CD8beta+ cells in patients who developed GVHD compared to those that did not. Although larger prospective clinical studies will be necessary to validate these results, this study demonstrates that high-content flow cytometry coupled with temporal analysis is a powerful approach for developing new diagnostic tools, and may be useful for developing a sensitive and specific predictive test for GVHD.

Subfields: Hematology, Public Health, Environmental and Occupational Health, Transplantation

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Citations in the corpus

• flowCore: a Bioconductor package for high throughput flow cytometry (2009, methodology): “The flowCore package has been successfully applied in the analysis of several data sets, both originating from clinical trials [1] and drug discovery experiments [9].”
• ASYMPTOTICS FOR GENERAL MULTIVARIATE KERNEL DENSITY DERIVATIVE ESTIMATORS (2011, methodology): “Figure 5 is a subset of data from the flow cytometry experiment described in Brinkman et al. (2007). The left panel is cellular fluorescence measurements – corresponding to antibodies CD4 and CD8β, after gating on CD3-positive cells – on a patient who develops graft-versus-host disease.”
• Combining Mixture Components for Clustering (2010, unknown): “We now apply our method to the GvHD data of Brinkman et al. (2007).”
• Generalizing to Unseen Domains: A Survey on Domain Generalization (2021, methodology): “The Graft-versus-host disease (GvHD) dataset [156] is also popular and is used to test several methods [25, 24] for the flow cytometry problem.”