An interactive reference framework for modeling a dynamic immune system

Multiple characteristics of individual cells define cell types and their physiological states. Spitzer et al. quantitated the abundance of 39 different cell surface proteins or transcription factors on individual cells of the mouse immune system. They used these measurements to create a map that clustered similar individual cells into groups corresponding to cell type and function. Their extensible experimental platform will allow the inclusion of other data types and data from independent laboratories. Science , this issue 10.1126/science.1259425 Cytometry meets mass spectrometry to create a functional map of the immune system. Immune cells function in an interacting hierarchy that coordinates the activities of various cell types according to genetic and environmental contexts. We developed graphical approaches to construct an extensible immune reference map from mass cytometry data of cells from different organs, incorporating landmark cell populations as flags on the map to compare cells from distinct samples. The maps recapitulated canonical cellular phenotypes and revealed reproducible, tissue-specific deviations. The approach revealed influences of genetic variation and circadian rhythms on immune system structure, enabled direct comparisons of murine and human blood cell phenotypes, and even enabled archival fluorescence-based flow cytometry data to be mapped onto the reference framework. This foundational reference map provides a working definition of systemic immune organization to which new data can be integrated to reveal deviations driven by genetics, environment, or pathology.