Saturday, 16 September 2017

A conceptual and computational framework ...

Our latest paper, in PLOS Computational Biology, is snappily titled:  A conceptual and computational framework for modelling and understanding the non-equilibrium gene regulatory networks of mouse embryonic stem cells.

Our author summary is:
Pluripotent stem cells possess the capacity both to renew themselves indefinitely and to differentiate to any cell type in the body. Thus the ability to direct stem cell differentiation would have immense potential in regenerative medicine. There is a massive amount of biological data relevant to stem cells; here we exploit data relating to stem cell differentiation to help understand cell behaviour and complexity. These cells contain a dynamic, non-equilibrium network of genes regulated in part by transcription factors expressed by the network itself. Here we take an existing theoretical framework, Transcription Factor Branching Processes, which explains how these genetic networks can have critical behaviour, and can tip between low and full expression. We use this theory as the basis for the design and implementation of a computational simulation platform, which we then use to run a variety of simulation experiments, to gain a better understanding how these various transcription factors can combine, interact, and influence each other. The simulation parameters are derived from experimental data relating to the core factors in pluripotent stem cell differentiation. The simulation results determine the critical values of branching process parameters, and how these are modulated by the various interacting transcription factors.

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