Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

CellRank for directed single-cell fate mapping

View ORCID ProfileMarius Lange, View ORCID ProfileVolker Bergen, Michal Klein, Manu Setty, Bernhard Reuter, View ORCID ProfileMostafa Bakhti, View ORCID ProfileHeiko Lickert, View ORCID ProfileMeshal Ansari, View ORCID ProfileJanine Schniering, Herbert B. Schiller, View ORCID ProfileDana Pe’er, View ORCID ProfileFabian J. Theis
doi: https://doi.org/10.1101/2020.10.19.345983
Marius Lange
1Institute of Computational Biology, Helmholtz Center Munich, Germany
2Department of Mathematics, Technical University of Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marius Lange
Volker Bergen
1Institute of Computational Biology, Helmholtz Center Munich, Germany
2Department of Mathematics, Technical University of Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Volker Bergen
Michal Klein
1Institute of Computational Biology, Helmholtz Center Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manu Setty
3Program for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernhard Reuter
4Department of Computer Science, University of Tübingen, Germany
5Zuse Institute Berlin (ZIB), Takustr. 7, 14195 Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mostafa Bakhti
6Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, Germany
7German Center for Diabetes Research (DZD), Neuherberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mostafa Bakhti
Heiko Lickert
6Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, Germany
7German Center for Diabetes Research (DZD), Neuherberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Heiko Lickert
Meshal Ansari
1Institute of Computational Biology, Helmholtz Center Munich, Germany
8Comprehensive Pneumology Center (CPC) / Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Meshal Ansari
Janine Schniering
8Comprehensive Pneumology Center (CPC) / Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Janine Schniering
Herbert B. Schiller
8Comprehensive Pneumology Center (CPC) / Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dana Pe’er
3Program for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Dana Pe’er
  • For correspondence: fabian.theis@helmholtz-muenchen.de peerd@mskcc.org
Fabian J. Theis
1Institute of Computational Biology, Helmholtz Center Munich, Germany
2Department of Mathematics, Technical University of Munich, Germany
9TUM School of Life Sciences Weihenstephan, Technical University of Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Fabian J. Theis
  • For correspondence: fabian.theis@helmholtz-muenchen.de peerd@mskcc.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Computational trajectory inference enables the reconstruction of cell-state dynamics from single-cell RNA sequencing experiments. However, trajectory inference requires that the direction of a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank (https://cellrank.org) for mapping the fate of single cells in diverse scenarios, including perturbations such as regeneration or disease, for which direction is unknown. Our approach combines the robustness of trajectory inference with directional information from RNA velocity, derived from ratios of spliced to unspliced reads. CellRank takes into account both the gradual and stochastic nature of cellular fate decisions, as well as uncertainty in RNA velocity vectors. On data from pancreas development, we show that it automatically detects initial, intermediate and terminal populations, predicts fate potentials and visualizes continuous gene expression trends along individual lineages. CellRank also predicts a novel dedifferentiation trajectory during regeneration after lung injury, which we follow up experimentally by confirming the existence of previously unknown intermediate cell states.

Competing Interest Statement

F.J.T. reports receiving consulting fees from Roche Diagnostics GmbH and Cellarity Inc., and ownership interest in Cellarity, Inc. and Dermagnostix.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted October 20, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
CellRank for directed single-cell fate mapping
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
CellRank for directed single-cell fate mapping
Marius Lange, Volker Bergen, Michal Klein, Manu Setty, Bernhard Reuter, Mostafa Bakhti, Heiko Lickert, Meshal Ansari, Janine Schniering, Herbert B. Schiller, Dana Pe’er, Fabian J. Theis
bioRxiv 2020.10.19.345983; doi: https://doi.org/10.1101/2020.10.19.345983
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
CellRank for directed single-cell fate mapping
Marius Lange, Volker Bergen, Michal Klein, Manu Setty, Bernhard Reuter, Mostafa Bakhti, Heiko Lickert, Meshal Ansari, Janine Schniering, Herbert B. Schiller, Dana Pe’er, Fabian J. Theis
bioRxiv 2020.10.19.345983; doi: https://doi.org/10.1101/2020.10.19.345983

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Bioinformatics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4113)
  • Biochemistry (8815)
  • Bioengineering (6518)
  • Bioinformatics (23459)
  • Biophysics (11789)
  • Cancer Biology (9207)
  • Cell Biology (13322)
  • Clinical Trials (138)
  • Developmental Biology (7436)
  • Ecology (11409)
  • Epidemiology (2066)
  • Evolutionary Biology (15149)
  • Genetics (10436)
  • Genomics (14043)
  • Immunology (9171)
  • Microbiology (22153)
  • Molecular Biology (8812)
  • Neuroscience (47566)
  • Paleontology (350)
  • Pathology (1428)
  • Pharmacology and Toxicology (2491)
  • Physiology (3730)
  • Plant Biology (8079)
  • Scientific Communication and Education (1437)
  • Synthetic Biology (2220)
  • Systems Biology (6037)
  • Zoology (1253)