Award details

CellBranch : a toolset for exploring Stem Cell Differentiation and Pluripotency with Branching Process Theory

Reference	BB/L018705/1
Principal Investigator / Supervisor	Professor Susan Stepney
Co-Investigators / Co-Supervisors	Professor Austin Smith
Institution	University of York
Department	Computer Science
Funding type	Research
Value (£)	140,314
Status	Completed
Type	Research Grant
Start date	24/03/2014
End date	30/06/2015
Duration	15 months

Abstract

One important biological application area is stem cell differentiation. Embryonic stem (ES) cells have the potential to produce all an animal's cell types: this is called pluripotency. In theory, stem cells could be directed to differentiate into any cell type, for therapeutic purposes. However, we cannot yet reliably direct their behaviour, and so cannot yet fully exploit this potential. To further our understanding of such biological systems, we need sophisticated tools to analyse the system's complexity and the vast amounts of data available. Computational tools provide an important route to gaining such understanding. We will exploit the established CoSMoS simulation approach, applied to an important theoretical framework, branching process theory (BPT). We will use BPT to model information flow based on genome-wide patterns of binding of key pluripotency transcription factors (TFs), capturing the expression of these TFs in terms of branching processes that propagate through time. Genome location data, which describe interactions between TFs and other genes at genome-wide scales, can be used to simulate these branching processes and estimate patterns of interference that give rise to individual cell trajectories. Here we will build computational models and simulation tools based on BPT, targeted to research questions in the domain of embryonic stem cell differentiation regulation, and epigenetic control, as informed by high throughput data sources. We will validate the tool by application to specific existing datasets. Tools need to be usable and accessible to benefit the wider community. We will make the fully documented tools available to the wider research community through York's HEFCE-funded YouShare "Software as a Service" portal.

Summary

Impact Summary

1. Branching Process Theory applied to Stem Cell Differentiation provides a novel theoretical framework for analysing an essential aspect of stem cell biology: how to understand complex multilayered high throughput data, and ultimately how better to control the development of stem cells into differentiated tissue. 2. CellBranch takes the impact of BPT from the theoretical to the practical domain. By providing an executable computational tool, BPT can be used to explore and analyse high volume data sets for greater biological understanding. 3. Deploying CellBranch through YouShare takes the impact from the individual laboratory to the entire community, by providing open access to the toolset, and compute resource to run the analyses. 4. By allowing the entire community access to the toolset and theory, we hasten the day that stem cell science is advanced enough to provide the promised therapeutic benefits to the world at large.

Committee	Research Committee C (Genes, development and STEM approaches to biology)
Research Topics	Stem Cells, Technology and Methods Development
Research Priority	X – Research Priority information not available
Research Initiative	Tools and Resources Development Fund (TRDF) [2006-2015]
Funding Scheme	X – not Funded via a specific Funding Scheme

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