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9 - Bayesian inference for model selection: an application to aberrant signalling pathways in chronic myeloid leukaemia

Published online by Cambridge University Press:  05 July 2015

By
Lisa E. M. Hopcroft ,
Ben Calderhead ,
Paolo Gallipoli ,
Tessa L. Holyoake  and
Mark A. Girolami
Edited by
Florian Markowetz  and
Michael Boutros
Lisa E. M. Hopcroft
Affiliation:
University of Glasgow
Ben Calderhead
Affiliation:
University College London
Paolo Gallipoli
Affiliation:
University of Glasgow
Tessa L. Holyoake
Affiliation:
University of Glasgow
Mark A. Girolami
Affiliation:
University College London
Florian Markowetz
Affiliation:
Cancer Research UK Cambridge Institute
Michael Boutros
Affiliation:
German Cancer Research Center, Heidelberg
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Summary

In the analysis of any data using statistical modelling, it is imperative that the choice of model is informed by expert knowledge and that its adequacy is determined based on the extent to which it captures and describes the patterns observed in the data. This is especially true in systems where a subset of the constituent components may not be known or cannot be observed. In this chapter, we demonstrate how statistical inference can be used to inform model selection and, by identifying where existing models are unable to sufficiently capture observed behaviour, that statistical inference can help indicate which model refinements may be required.

In this chapter, we use Bayesian statistical methodology – specifically, Riemannian manifold population MCMC – to model interactions between molecular species in the JAK/STAT pathway in chronic myeloid leukaemia (CML) and compare two candidate models. We set out the biological context for this inference in Sections 9.1–9.1.4 and describe the two candidate models in Section 9.3. With the biology established, we describe our statistical methodology (Section 9.4) which we successfully apply in a simulation study to provide a proof of concept (Section 9.5), before we consider a subsequent, more biologically realistic dataset (Section 9.6) to assess which model best describes the behaviour observed in vitro. We relate the findings from this second synthetic study back to our model and dataset construction, thereby highlighting what further in vitro and in silico work is required (Section 9.7).

The oncology of chronic myeloid leukaemia

The condition that we now recognise as chronic myeloid leukaemia (CML) was first described in 1845, in quick succession, by two pathologists, Dr John Hughes Bennett (Bennett 1845) and Dr Rudolf Virchow (Virchow 1845).

Type
Chapter
Information
Systems Genetics
Linking Genotypes and Phenotypes
 , pp. 161 - 190
Publisher: Cambridge University Press
Print publication year: 2015

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