CytoMAP: A Spatial Analysis Toolbox Reveals Features of Myeloid Cell Organization in Lymphoid Tissues
Caleb R. Stoltzfus,
Jakub Filipek,
Benjamin H. Gern,
Brandy E. Olin,
Joseph M. Leal,
Yajun Wu,
Miranda R. Lyons-Cohen,
Jessica Y. Huang,
Clarissa L. Paz-Stoltzfus,
Courtney R. Plumlee,
Thomas Pöschinger,
Kevin B. Urdahl,
Mario Perro,
Michael Y. Gerner
Affiliations
Caleb R. Stoltzfus
Department of Immunology, University of Washington, Seattle, WA 98109, USA
Jakub Filipek
Department of Immunology, University of Washington, Seattle, WA 98109, USA
Benjamin H. Gern
Seattle Children’s Research Institute, Seattle, WA 98109, USA; Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
Brandy E. Olin
Department of Immunology, University of Washington, Seattle, WA 98109, USA
Joseph M. Leal
Department of Immunology, University of Washington, Seattle, WA 98109, USA
Yajun Wu
Department of Immunology, University of Washington, Seattle, WA 98109, USA
Miranda R. Lyons-Cohen
Department of Immunology, University of Washington, Seattle, WA 98109, USA
Jessica Y. Huang
Department of Immunology, University of Washington, Seattle, WA 98109, USA
Clarissa L. Paz-Stoltzfus
School of Medicine, University of Washington, Seattle, WA 98195, USA
Courtney R. Plumlee
Seattle Children’s Research Institute, Seattle, WA 98109, USA
Thomas Pöschinger
Roche Innovation Center Munich, Pharmaceutical Research & Early Development (pRED), Discovery Pharmacology, Nonnenwald 2, 82377 Penzberg, Germany
Kevin B. Urdahl
Department of Immunology, University of Washington, Seattle, WA 98109, USA; Seattle Children’s Research Institute, Seattle, WA 98109, USA; Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
Mario Perro
Roche Innovation Center Zurich, Pharmaceutical Research & Early Development (pRED), Wagistrasse 10, 8952 Schlieren, Switzerland
Michael Y. Gerner
Department of Immunology, University of Washington, Seattle, WA 98109, USA; Corresponding author
Summary: Recently developed approaches for highly multiplexed imaging have revealed complex patterns of cellular positioning and cell-cell interactions with important roles in both cellular- and tissue-level physiology. However, tools to quantitatively study cellular patterning and tissue architecture are currently lacking. Here, we develop a spatial analysis toolbox, the histo-cytometric multidimensional analysis pipeline (CytoMAP), which incorporates data clustering, positional correlation, dimensionality reduction, and 2D/3D region reconstruction to identify localized cellular networks and reveal features of tissue organization. We apply CytoMAP to study the microanatomy of innate immune subsets in murine lymph nodes (LNs) and reveal mutually exclusive segregation of migratory dendritic cells (DCs), regionalized compartmentalization of SIRPα− dermal DCs, and preferential association of resident DCs with select LN vasculature. The findings provide insights into the organization of myeloid cells in LNs and demonstrate that CytoMAP is a comprehensive analytics toolbox for revealing features of tissue organization in imaging datasets. : Stoltzfus et al. present CytoMAP, a spatial analytics platform that incorporates diverse statistical and visualization modules for analysis of cellular positioning, cell-cell interactions, global tissue structure, and heterogeneity of tissue microenvironments. Exploration of myeloid cell localization in lymph nodes reveals fundamental positional relationships between dendritic cell subsets and local vasculature. Keywords: spatial analysis, dendritic cell positioning, quantitative microscopy, machine learning, lymphoid tissue anatomy, quantitative image analysis, tissue microanatomy, tissue organization, tumor microenvironments, cellular organization