Automated Mapping of Phenotype Space with Single-Cell Data

Accurate and rapid identification of cell populations is key to discovering novelty in multidimensional single cell experiments. We present a population finding algorithm X-shift that can process large datasets using fast KNN estimation of cell event density and automatically arranges populations by a marker-based classification system. X-shift analysis of mouse bone marrow data resolved the majority of known and several previously undescribed cell populations. Interestingly, previously known cell populations, as well as intermediate cell populations in early hematopoietic development, were described via novel marker combinations that were defined via routes to their locations in expressed marker space. X-shift provides a rapid, reliable approach to managed cell subset analysis that maximizes automation that not only best mimics human intuition, but as we show provides access to novel insights that “prior knowledge” might prevent the researcher from visualizing.