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Modelling: Big Data and Society Conference
A new PhD student publication
Dr. Simon Moon
Simon’s work during his time in CoMPLEX focused on cell division history. Usually, Cell division history can be examined with the fluorescent dye: 5- (and 6-) carboxyflourescein diacetate succinimidyl ester (CFSE). Modelling the data produced by flow cytometric analysis of CFSE has recently been an active area of research and promises to give new insight into the behaviour of dividing populations of cells.
Simon’s work describes how CFSE data can be modelled with discrete time multi-type branching processes. This approach had not previously been used where CFSE data is concerned, although branching process models of cell division had an established history of producing simple tractable models that yield biologically relevant results. In particular, he suggested these models could be adapted to staged behaviour. Simon uses a multi-type model in an attempt to isolate the phenotypic stage at which negative selection occurs in the thymus. In doing so he re-examine published experimental data that analyses the fate of positively selected double positive (DP CD69+) thymocytes during and after their transition to single positive (SP) stage. He also analyzed the data with respect to two alternative hypotheses:
- 1. Death occurs at the DP CD69+ stage and not at the SP stage
- 2. Death occurs at the SP stage and not at the DP CD69+ stage and it occurs concurrently with division.
Simon concluded that the second model fitted the data better than the first. Motivated to avoid the discrete time assumption that division behaviour is synchronous, Simon’s work shows how a continuous time branching process model of CFSE can be obtained. The results of a subsequent re-analysis of the published data conflicted with his discrete time modelling. Upon further investigation, he concluded that the continuous time model was a poorer model of the data. Finally, he also modelled the effect of negative selection in combination with division on the thymocyte repertoire with a discrete time branching process. The results of his analysis suggest that there may be an advantage to division and selection being a combined process.
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