Exploration of Cell Development Pathways through High-Dimensional Single Cell Analysis in Trajectory Space
Denis Dermadi,
Michael Bscheider,
Kristina Bjegovic,
Nicole H. Lazarus,
Agata Szade,
Husein Hadeiba,
Eugene C. Butcher
Affiliations
Denis Dermadi
Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System and the Palo Alto Veterans Institute for Research (PAVIR), Palo Alto, CA 94304, USA; Corresponding author
Michael Bscheider
Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System and the Palo Alto Veterans Institute for Research (PAVIR), Palo Alto, CA 94304, USA
Kristina Bjegovic
The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System and the Palo Alto Veterans Institute for Research (PAVIR), Palo Alto, CA 94304, USA
Nicole H. Lazarus
Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System and the Palo Alto Veterans Institute for Research (PAVIR), Palo Alto, CA 94304, USA
Agata Szade
Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System and the Palo Alto Veterans Institute for Research (PAVIR), Palo Alto, CA 94304, USA
Husein Hadeiba
The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System and the Palo Alto Veterans Institute for Research (PAVIR), Palo Alto, CA 94304, USA
Eugene C. Butcher
Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System and the Palo Alto Veterans Institute for Research (PAVIR), Palo Alto, CA 94304, USA; Corresponding author
Summary: High-dimensional single cell profiling coupled with computational modeling is emerging as a powerful tool to elucidate developmental programs directing cell lineages. We introduce tSpace, an algorithm based on the concept of “trajectory space”, in which cells are defined by their distance along nearest neighbor pathways to every other cell in a population. Graphical mapping of cells in trajectory space allows unsupervised reconstruction and exploration of complex developmental sequences. Applied to flow and mass cytometry data, the method faithfully reconstructs thymic T cell development and reveals development and trafficking regulation of tonsillar B cells. Applied to the single cell transcriptome of mouse intestine and C. elegans, the method recapitulates development from intestinal stem cells to specialized epithelial phenotypes more faithfully than existing algorithms and orders C. elegans cells concordantly to the associated embryonic time. tSpace profiling of complex populations is well suited for hypothesis generation in developing cell systems. : Developmental Biology; Systems Biology; In Silico Biology Subject Areas: Developmental Biology, Systems Biology, In Silico Biology
