dc.creator | Herring, Charles Albert | |
dc.date.accessioned | 2020-08-22T00:16:56Z | |
dc.date.available | 2018-04-10 | |
dc.date.issued | 2018-04-10 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-03302018-121504 | |
dc.identifier.uri | http://hdl.handle.net/1803/11790 | |
dc.description.abstract | Modern single-cell technologies allow multiplexed sampling of cellular states within a tissue. However, computational tools that can infer developmental cell-state transitions reproducibly from such single-cell data are lacking. Here, introduced is p-Creode, an unsupervised algorithm that produces multi-branching graphs from single-cell data, compares graphs with differing topologies, and infers a statistically robust hierarchy of cell-state transitions that define developmental trajectories. p-Creode is applied to mass cytometry, multiplex immunofluorescence, and single-cell RNA-seq data. As a test case, we validate cell-state-transition trajectories predicted by p-Creode for intestinal tuft cells, a rare, chemosensory cell type. We clarify that tuft cells are specified outside of the Atoh1-dependent secretory lineage in the small intestine. However, p-Creode also predicts, and we confirm, that tuft cells arise from an alternative, Atoh1-driven developmental program in the colon. These studies introduce p-Creode as a reliable method for analyzing large datasets that depict branching transition trajectories. | |
dc.format.mimetype | application/pdf | |
dc.subject | differentiation hierarchies | |
dc.subject | trajectories | |
dc.subject | pseudo-time analysis | |
dc.subject | single-cell RNA-seq | |
dc.subject | intestine and colon | |
dc.subject | mass cytometry | |
dc.subject | graph theory | |
dc.subject | tuft cells | |
dc.subject | cell-state transitions | |
dc.subject | single-cell biology | |
dc.title | Cell Fate Relationships Mapped by p-Creode Trajectory Analysis of Single-cell Data | |
dc.type | dissertation | |
dc.contributor.committeeMember | John Anthony Capra | |
dc.contributor.committeeMember | Erin Rericha | |
dc.contributor.committeeMember | Ken Lau | |
dc.contributor.committeeMember | Gregor Neuert | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Chemical and Physical Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2018-04-10 | |
local.embargo.lift | 2018-04-10 | |
dc.contributor.committeeChair | Vito Quaranta | |