Approximated gene expression trajectories for gene regulatory network inference on cell tracks
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.
Authors
- Kane Toh (ORCID: https://orcid.org/0000-0001-6882-1110)
- Benjamin John Steventon (ORCID: https://orcid.org/0000-0001-7838-839X)
- Kay Spiess
- Timothy Fulton (ORCID: https://orcid.org/0000-0002-0386-1821)
- Yuxuan Wang (ORCID: https://orcid.org/0000-0001-9117-0619)
- Dillan Saunders (ORCID: https://orcid.org/0000-0001-5169-5488)
- Brooks Paige (ORCID: https://orcid.org/0000-0002-4797-1563)
- Seongwon Hwang (ORCID: https://orcid.org/0000-0003-0805-3708)
- Berta Verd (ORCID: https://orcid.org/0000-0001-9835-009X)
- Shannon E. Taylor (ORCID: https://orcid.org/0000-0003-3490-3307)
Institutions
- University of Cambridge (GB)
- University of Oxford (GB)
- The Alan Turing Institute (GB)
- University College London (GB)
Publication Details
- Journal
- iScience
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1016/j.isci.2024.110840
- Citations
- 5
- Primary Topic
- Gene Regulatory Network Analysis
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- Wellcome Trust
- Alan Turing Institute
- UK Research and Innovation
- Royal Society
- University of Cambridge
- University College London
- University of Oxford
- Cambridge Trust
- Gates Cambridge Trust
- Engineering and Physical Sciences Research Council
- St Catharine's College, University of Cambridge