Hierarchical cell-type identifier accurately distinguishes immune-cell subtypes enabling precise profiling of tissue microenvironment with single-cell RNA-sequencing

Abstract

AO_SCPLOWBSTRACTC_SCPLOWSingle-cell RNA-seq enabled in-depth study on tissue micro-environment and immune-profiling, where a crucial step is to annotate cell identity. Immune cells play key roles in many diseases while their activities are hard to track due to diverse and highly variable nature. Existing cell-type identifiers had limited performance for this purpose. We present HiCAT, a hierarchical, marker-based cell-type identifier utilizing gene set analysis for statistical scoring for given markers. It features successive identification of major-type, minor-type and subsets utilizing subset markers structured in a three-level taxonomy tree. Comparison with manual annotation and pairwise match test showed HiCAT outperforms others in major- and minor-type identification. For subsets, we qualitatively evaluated marker expression profile demonstrating that HiCAT provide most clear immune cell landscape. HiCAT was also used for immune cell profiling in ulcerative colitis and discovered distinct features of the disease in macrophage and T cell subsets that could not be identified previously.