CoSpar identifies early cell fate biases from single-cell transcriptomic and lineage information.


Journal

Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648

Informations de publication

Date de publication:
07 2022
Historique:
received: 06 05 2021
accepted: 04 01 2022
pubmed: 23 2 2022
medline: 20 7 2022
entrez: 22 2 2022
Statut: ppublish

Résumé

A goal of single-cell genome-wide profiling is to reconstruct dynamic transitions during cell differentiation, disease onset and drug response. Single-cell assays have recently been integrated with lineage tracing, a set of methods that identify cells of common ancestry to establish bona fide dynamic relationships between cell states. These integrated methods have revealed unappreciated cell dynamics, but their analysis faces recurrent challenges arising from noisy, dispersed lineage data. In this study, we developed coherent, sparse optimization (CoSpar) as a robust computational approach to infer cell dynamics from single-cell transcriptomics integrated with lineage tracing. Built on assumptions of coherence and sparsity of transition maps, CoSpar is robust to severe downsampling and dispersion of lineage data, which enables simpler experimental designs and requires less calibration. In datasets representing hematopoiesis, reprogramming and directed differentiation, CoSpar identifies early fate biases not previously detected, predicting transcription factors and receptors implicated in fate choice. Documentation and detailed examples for common experimental designs are available at https://cospar.readthedocs.io/ .

Identifiants

pubmed: 35190690
doi: 10.1038/s41587-022-01209-1
pii: 10.1038/s41587-022-01209-1
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1066-1074

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL095993
Pays : United States
Organisme : NCATS NIH HHS
ID : U01 TR001810
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92020C00005
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA218579
Pays : United States

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Shou-Wen Wang (SW)

Department of Systems Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. shouwen_wang@hms.harvard.edu.

Michael J Herriges (MJ)

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

Kilian Hurley (K)

Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
Tissue Engineering Research Group, Royal College of Surgeons in Ireland, Dublin, Ireland.

Darrell N Kotton (DN)

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

Allon M Klein (AM)

Department of Systems Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. allon_klein@hms.harvard.edu.

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