PT - JOURNAL ARTICLE AU - Weber, Lukas M. AU - Nowicka, Malgorzata AU - Soneson, Charlotte AU - Robinson, Mark D. TI - diffcyt: Differential discovery in high-dimensional cytometry via high-resolution clustering AID - 10.1101/349738 DP - 2019 Jan 01 TA - bioRxiv PG - 349738 4099 - http://biorxiv.org/content/early/2019/03/29/349738.short 4100 - http://biorxiv.org/content/early/2019/03/29/349738.full AB - High-dimensional flow and mass cytometry allow cell types and states to be characterized in great detail by measuring expression levels of more than 40 targeted protein markers per cell at the single-cell level. However, data analysis can be difficult, due to the large size and dimensionality of datasets as well as limitations of existing computational methods. Here, we present diffcyt, a new computational framework for differential discovery analyses in high-dimensional cytometry data, based on a combination of high-resolution clustering and empirical Bayes moderated tests adapted from transcriptomics. Our approach provides improved statistical performance, including for rare cell populations, along with flexible experimental designs and fast runtimes in an open-source framework.