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Semi-Supervised Non-Parametric Bayesian Modelling of Spatial Proteomics.

Accepted version
Peer-reviewed

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Authors

Crook, Oliver M 
Lilley, Kathryn S 
Gatto, Laurent 
Kirk, Paul DW 

Abstract

Understanding sub-cellular protein localisation is an essential component in the analysis of context specific protein function. Recent advances in quantitative mass-spectrometry (MS) have led to high resolution mapping of thousands of proteins to sub-cellular locations within the cell. Novel modelling considerations to capture the complex nature of these data are thus necessary. We approach analysis of spatial proteomics data in a non-parametric Bayesian framework, using K-component mixtures of Gaussian process regression models. The Gaussian process regression model accounts for correlation structure within a sub-cellular niche, with each mixture component capturing the distinct correlation structure observed within each niche. The availability of marker proteins (i.e. proteins with a priori known labelled locations) motivates a semi-supervised learning approach to inform the Gaussian process hyperparameters. We moreover provide an efficient Hamiltonian-within-Gibbs sampler for our model. Furthermore, we reduce the computational burden associated with inversion of covariance matrices by exploiting the structure in the covariance matrix. A tensor decomposition of our covariance matrices allows extended Trench and Durbin algorithms to be applied to reduce the computational complexity of inversion and hence accelerate computation. We provide detailed case-studies on Drosophila embryos and mouse pluripotent embryonic stem cells to illustrate the benefit of semi-supervised functional Bayesian modelling of the data.

Description

Keywords

Bayesian mixture models, proteomics, semi-supervised learning

Journal Title

Ann Appl Stat

Conference Name

Journal ISSN

1932-6157
1941-7330

Volume Title

Publisher

Institute of Mathematical Statistics
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/N023129/1)
Wellcome Trust (110170/Z/15/Z)