Assessing differential cell composition in single-cell studies using voomCLR

In single-cell studies, a common question is whether there is a change in cell composition between conditions. While ideally, one needs absolute cell counts (number of cells per volumetric unit in a sample) to address these questions, current experimentation typically obtains cell counts that only carry relative information. It is therefore crucial to account for the compositional nature of cell count data in the statistical analysis. While recently developed methods address compositionality using compositional transformations together with a bias correction, they do not account for the uncertainty involved in estimation of the bias term, nor do they accommodate the mean-variance structure of the counts. Here, we introduce a statistical method, voomCLR, for assessing differences in cell composition between conditions incorporating both uncertainty on the bias term as well as acknowledging the mean-variance structure of the transformed data, by leveraging developments from the differential gene expression literature. We demonstrate the performances of voomCLR, illustrate the benefit of all components and compare the methodology to the state-of-the-art on simulated and real single-cell gene expression datasets.