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A Bayesian mixture modelling approach for spatial proteomics.

ABSTRACT: Analysis of the spatial sub-cellular distribution of proteins is of vital importance to fully understand context specific protein function. Some proteins can be found with a single location within a cell, but up to half of proteins may reside in multiple locations, can dynamically re-localise, or reside within an unknown functional compartment. These considerations lead to uncertainty in associating a protein to a single location. Currently, mass spectrometry (MS) based spatial proteomics relies on supervised machine learning algorithms to assign proteins to sub-cellular locations based on common gradient profiles. However, such methods fail to quantify uncertainty associated with sub-cellular class assignment. Here we reformulate the framework on which we perform statistical analysis. We propose a Bayesian generative classifier based on Gaussian mixture models to assign proteins probabilistically to sub-cellular niches, thus proteins have a probability distribution over sub-cellular locations, with Bayesian computation performed using the expectation-maximisation (EM) algorithm, as well as Markov-chain Monte-Carlo (MCMC). Our methodology allows proteome-wide uncertainty quantification, thus adding a further layer to the analysis of spatial proteomics. Our framework is flexible, allowing many different systems to be analysed and reveals new modelling opportunities for spatial proteomics. We find our methods perform competitively with current state-of-the art machine learning methods, whilst simultaneously providing more information. We highlight several examples where classification based on the support vector machine is unable to make any conclusions, while uncertainty quantification using our approach provides biologically intriguing results. To our knowledge this is the first Bayesian model of MS-based spatial proteomics data.

SUBMITTER: Crook OM

PROVIDER: S-EPMC6258510 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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A Bayesian mixture modelling approach for spatial proteomics.

Crook Oliver M OM Mulvey Claire M CM Kirk Paul D W PDW Lilley Kathryn S KS Gatto Laurent L

PLoS computational biology 20181127 11

Analysis of the spatial sub-cellular distribution of proteins is of vital importance to fully understand context specific protein function. Some proteins can be found with a single location within a cell, but up to half of proteins may reside in multiple locations, can dynamically re-localise, or reside within an unknown functional compartment. These considerations lead to uncertainty in associating a protein to a single location. Currently, mass spectrometry (MS) based spatial proteomics relies ...[more]

PMID: 30481170

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Project description:BackgroundChildren's early development plays a vital role for maintaining healthy lives and influences future outcomes. It is also heavily affected by community factors which vary geographically. Direct methods do not provide a comprehensive picture of this variation, especially for areas with sparse populations and low data coverage. In the context of Australia, the Australian Early Development Census (AEDC) provides a measure of early child development upon school entry. There are two primary aims of this study: (i) provide improved prevalence estimates of children who are considered as developmentally vulnerable in regions across Australia; (ii) ascertain how social-economic disadvantage partly explains the spatial variation.MethodsWe used Bayesian spatial hierarchical models with the Socio-economic Indexes for Areas (SEIFA) as a covariate to provide improved estimates of all 335 SA3 regions in Australia. The study included 308,953 children involved in the 2018 AEDC where 21.7% of them were considered to be developmentally vulnerable in at least one domain. There are five domains of developmental vulnerability-physical health and wellbeing; social competence; emotional maturity; language and cognitive skills; and communication and general knowledge.ResultsThere are significant improvements in estimation of the prevalence of developmental vulnerability through incorporating the socio-economic disadvantage in an area. These improvements persist in all five domains-the largest improvements occurred in the Language and Cognitive Skills domain. In addition, our results reveal that there is an important geographical dimension to developmental vulnerability in Australia.ConclusionSparsely populated areas in sample surveys lead to unreliable direct estimates of the relatively small prevalence of child vulnerability. Bayesian spatial modelling can account for the spatial patterns in childhood vulnerability while including the impact of socio-economic disadvantage on geographic variation. Further investigation, using a broader range of covariates, could shed more light on explaining this spatial variation.

Dataset Information

A Bayesian mixture modelling approach for spatial proteomics.

Publications

A Bayesian mixture modelling approach for spatial proteomics.

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