Characterization of cell fate probabilities in single-cell data with Palantir Journal Article

Authors: Setty, M.; Kiseliovas, V.; Levine, J.; Gayoso, A.; Mazutis, L.; Pe'er, D.
Article Title: Characterization of cell fate probabilities in single-cell data with Palantir
Abstract: Single-cell RNA sequencing studies of differentiating systems have raised fundamental questions regarding the discrete versus continuous nature of both differentiation and cell fate. Here we present Palantir, an algorithm that models trajectories of differentiating cells by treating cell fate as a probabilistic process and leverages entropy to measure cell plasticity along the trajectory. Palantir generates a high-resolution pseudo-time ordering of cells and, for each cell state, assigns a probability of differentiating into each terminal state. We apply our algorithm to human bone marrow single-cell RNA sequencing data and detect important landmarks of hematopoietic differentiation. Palantir’s resolution enables the identification of key transcription factors that drive lineage fate choice and closely track when cells lose plasticity. We show that Palantir outperforms existing algorithms in identifying cell lineages and recapitulating gene expression trends during differentiation, is generalizable to diverse tissue types, and is well-suited to resolving less-studied differentiating systems. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Keywords: nonhuman; comparative study; cytology; gene expression; transcription factor; cell fate; cell differentiation; cell lineage; rna; algorithm; probability; transcription; hematopoiesis; upregulation; bioinformatics; high resolution; colon; rna sequence; plasticity; single cell analysis; cell plasticity; tissue types; entropy; human; priority journal; article; digital storage; rna sequencing; markov chain; human bone marrow; probabilistic process; terminal state; time ordering; palantir
Journal Title: Nature Biotechnology
Volume: 37
Issue: 4
ISSN: 1087-0156
Publisher: Nature Publishing Group  
Date Published: 2019-04-01
Start Page: 451
End Page: 460
Language: English
DOI: 10.1038/s41587-019-0068-4
PUBMED: 30899105
PROVIDER: scopus
Notes: Erratum issued, see DOI: 10.1038/s41587-019-0282-0 -- Source: Scopus
Citation Impact
MSK Authors
  1. Manu Setty
    26 Setty
  2. Jacob H Levine
    7 Levine
  3. Dana Pe'er
    42 Pe'er
  4. Linas Mazutis
    16 Mazutis
  5. Adam J. Gayoso
    1 Gayoso