scTOP: physics-inspired order parameters for cellular identification and visualization.

Cell types Computational method Developmental trajectory Differentiation Single-cell RNA sequencing

Journal

Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744

Informations de publication

Date de publication:
01 11 2023
Historique:
received: 11 04 2023
accepted: 11 09 2023
pmc-release: 03 11 2024
medline: 6 11 2023
pubmed: 27 9 2023
entrez: 27 9 2023
Statut: ppublish

Résumé

Advances in single-cell RNA sequencing provide an unprecedented window into cellular identity. The abundance of data requires new theoretical and computational frameworks to analyze the dynamics of differentiation and integrate knowledge from cell atlases. We present 'single-cell Type Order Parameters' (scTOP): a statistical, physics-inspired approach for quantifying cell identity given a reference basis of cell types. scTOP can accurately classify cells, visualize developmental trajectories and assess the fidelity of engineered cells. Importantly, scTOP does this without feature selection, statistical fitting or dimensional reduction (e.g. uniform manifold approximation and projection, principle components analysis, etc.). We illustrate the power of scTOP using human and mouse datasets. By reanalyzing mouse lung data, we characterize a transient hybrid alveolar type 1/alveolar type 2 cell population. Visualizations of lineage tracing hematopoiesis data using scTOP confirm that a single clone can give rise to multiple mature cell types. We assess the transcriptional similarity between endogenous and donor-derived cells in the context of murine pulmonary cell transplantation. Our results suggest that physics-inspired order parameters can be an important tool for understanding differentiation and characterizing engineered cells. scTOP is available as an easy-to-use Python package.

Identifiants

pubmed: 37756586
pii: 329502
doi: 10.1242/dev.201873
pmc: PMC10629677
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL158965
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM119461
Pays : United States
Organisme : NIGMS NIH HHS
ID : 1R35GM119461
Pays : United States
Organisme : NIH HHS
ID : R01 HL158965-01
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2023. Published by The Company of Biologists Ltd.

Déclaration de conflit d'intérêts

Competing interests The authors declare no competing or financial interests.

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Auteurs

Maria Yampolskaya (M)

Department of Physics, Boston University, Boston, MA 02215, USA.

Michael J Herriges (MJ)

Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

Laertis Ikonomou (L)

Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY 14215, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University at Buffalo, The State University of New York, Buffalo, NY 14215, USA.

Darrell N Kotton (DN)

Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

Pankaj Mehta (P)

Department of Physics, Boston University, Boston, MA 02215, USA.
Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
Faculty of Computing and Data Science, Boston University, Boston, MA 02215, USA.
Biological Design Center, Boston University, Boston, MA 02215, USA.

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Classifications MeSH