RESUMEN
Automated clustering workflows are increasingly used for the analysis of high parameter flow cytometry data. This trend calls for algorithms which are able to quickly process tens of millions of data points, to compare results across subjects or time points, and to provide easily actionable interpretations of the results. To this end, we created Tailor, a model-based clustering algorithm specialized for flow cytometry data. Our approach leverages a phenotype-aware binning scheme to provide a coarse model of the data, which is then refined using a multivariate Gaussian mixture model. We benchmark Tailor using a simulation study and two flow cytometry data sets, and show that the results are robust to moderate departures from normality and inter-sample variation. Moreover, Tailor provides automated, non-overlapping annotations of its clusters, which facilitates interpretation of results and downstream analysis. Tailor is released as an R package, and the source code is publicly available at www.github.com/matei-ionita/Tailor.
Asunto(s)
Algoritmos , Programas Informáticos , Análisis por Conglomerados , Citometría de Flujo , Humanos , Distribución NormalRESUMEN
Resting CD4(+) T cells are the best-defined reservoir of latent human immunodeficiency virus type 1 (HIV-1) infection, but how the reservoir is formed is unclear. Understanding how the reservoir of latently infected cells forms is critical because it is a major barrier to curing HIV infection. The system described here may provide an in vitro model of latent HIV-1 infection in resting CD4(+) T cells. We demonstrated that HIV-1 integrates into the genomes of in vitro-inoculated resting CD4(+) T cells that have not received activating stimuli and have not entered cell cycle stage G(1b). A percentage of the resting CD4(+) T cells that contain integrated DNA produce virus upon stimulation, i.e., are latently infected. Our results show that latent HIV-1 infection occurs in unstimulated resting CD4(+) T cells and suggest a new route for HIV-1 reservoir formation.