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Approximated gene expression trajectories for gene regulatory network inference on cell tracks

Abstract:
The study of pattern formation has benefited from our ability to reverse-engineer gene regulatory network (GRN) structure from spatiotemporal quantitative gene expression data. Traditional approaches have focused on systems where the timescales of pattern formation and morphogenesis can be separated. Unfortunately, this is not the case in most animal patterning systems, where pattern formation and morphogenesis are co-occurring and tightly linked. To elucidate patterning mechanisms in such systems we need to adapt our GRN inference methodologies to include cell movements. In this work, we fill this gap by integrating quantitative data from live and fixed embryos to approximate gene expression trajectories (AGETs) in single cells and use these to reverse-engineer GRNs. This framework generates candidate GRNs that recapitulate pattern at the tissue level, gene expression dynamics at the single cell level, recover known genetic interactions and recapitulate experimental perturbations while incorporating cell movements explicitly for the first time.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.isci.2024.110840

Authors

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Institution:
University of Oxford
Division:
MPLS
Department:
Biology
Role:
Author


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Funder identifier:
https://ror.org/03wnrjx87
Grant:
109408/Z/15/Z, jointly funded with Wellcome Trust
Programme:
Henry Dale Fellowship
More from this funder
Funder identifier:
https://ror.org/0472cxd90
Grant:
101163722
Programme:
StG COUNTS
More from this funder
Funder identifier:
https://ror.org/029chgv08
Grant:
222279/Z/20/Z
Programme:
Developmental Mechanisms PhD studentship
More from this funder
Funder identifier:
https://ror.org/001aqnf71
Grant:
EP/T001569/1


Publisher:
Cell Press
Journal:
iScience More from this journal
Volume:
27
Issue:
9
Article number:
110840
Place of publication:
United States
Publication date:
2024-08-30
Acceptance date:
2024-08-21
DOI:
EISSN:
2589-0042
Pmid:
39290835


Language:
English
Pubs id:
2026302
Local pid:
pubs:2026302
Deposit date:
2025-05-01
ARK identifier:

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