Censcyt: censored covariates in differential abundance analysis in cytometry

Abstract

BackgroundInnovations in single cell technologies have lead to a flurry of datasets and computational tools to process and interpret them, including analyses of cell composition changes and transition in cell states. The diffcyt workflow for differential discovery in cytometry data consist of several steps, including preprocessing, cell population identification and differential testing for an association with a binary or continuous covariate. However, the commonly measured quantity of survival time in clinical studies often results in a censored covariate where classical differential testing is inapplicable.ResultsTo overcome this limitation, multiple methods to directly include censored covariates in differential abundance analysis were examined with the use of simulation studies and a case study. Results show that multiple imputation based methods offer on-par performance with the Cox proportional hazards model in terms of sensitivity and error control, while offering flexibility to account for covariates. The tested methods are implemented in the R package censcyt as an extension of diffcyt and are available at https://bioconductor.org/packages/censcyt.ConclusionMethods for the direct inclusion of a censored variable as a predictor in GLMMs are a valid alternative to classical survival analysis methods, such as the Cox proportional hazard model, while allowing for more flexibility in the differential analysis.