title: Wishbone identifies bifurcating developmental trajectories from single-cell data.
abstract: Recent single-cell analysis technologies offer an unprecedented opportunity to elucidate developmental pathways. Here we present Wishbone, an algorithm for positioning single cells along bifurcating developmental trajectories with high resolution. Wishbone uses multi-dimensional single-cell data, such as mass cytometry or RNA-Seq data, as input and orders cells according to their developmental progression, and it pinpoints bifurcation points by labeling each cell as pre-bifurcation or as one of two post-bifurcation cell fates. Using 30-channel mass cytometry data, we show that Wishbone accurately recovers the known stages of T-cell development in the mouse thymus, including the bifurcation point. We also apply the algorithm to mouse myeloid differentiation and demonstrate its generalization to additional lineages. A comparison of Wishbone to diffusion maps, SCUBA and Monocle shows that it outperforms these methods both in the accuracy of ordering cells and in the correct identification of branch points.
authors.affiliation: Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, New York, USA.
authors.forename: Manu
authors.initials: M
authors.lastname: Setty
authors.affiliation: Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, New York, USA.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tadmor
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Reich-Zeliger
authors.affiliation: Department of Mathematics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Omer
authors.initials: O
authors.lastname: Angel
authors.affiliation: Biological Services Unit, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Tomer Meir
authors.initials: TM
authors.lastname: Salame
authors.affiliation: Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, New York, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Kathail
authors.affiliation: Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, New York, USA.
authors.forename: Kristy
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Pathology, Stanford University, Stanford, California, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Bendall
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
authors.affiliation: Department of Biological Sciences, Department of Systems Biology, Columbia University, New York, New York, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Pe'er
mesh_terms: D000465:Algorithms; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D003198:Computer Simulation; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D012984:Software; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology*