Combinatorial prediction of marker panels from single‐cell transcriptomic data

Single-cell transcriptomic studies are identifying novel cell populations with exciting functional roles in various in vivo contexts, but identification of succinct gene marker panels for such populations remains a challenge. In this work, we introduce COMET, a computational framework for the identification of candidate marker panels consisting of one or more genes for cell populations of interest identified with single-cell RNA-seq data. We show that COMET outperforms other methods for the identification of single-gene panels and enables, for the first time, prediction of multi-gene marker panels ranked by relevance. Staining by flow cytometry assay confirmed the accuracy of COMET's predictions in identifying marker panels for cellular subtypes, at both the single- and multi-gene levels, validating COMET's applicability and accuracy in predicting favorable marker panels from transcriptomic input. COMET is a general non-parametric statistical framework and can be used as-is on various high-throughput datasets in addition to single-cell RNA-sequencing data. COMET is available for use via a web interface (http://www.cometsc.com/) or a stand-alone software package (https://github.com/MSingerLab/COMETSC). ; National Institute of Allergy and Infectious Diseases (U.S.) (Award P01AI129880)