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Inferring differential subcellular localisation in comparative spatial proteomics using BANDLE

Published version
Peer-reviewed

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Authors

Crook, oliver 
Breckels, lisa 
Kirk, paul 
christopher, josie 

Abstract

The steady-state localisation of proteins provides vital insight into their function. These localisations are context speci c with proteins translocating between di erent subcellular niches upon perturbation of the subcellular environment. Di erential localisation, that is a change in the steady-state subcellular location of a protein, provides a step towards mechanistic in- sight of subcellular protein dynamics. High-accuracy high-throughput mass spectrometry-based methods now exist to map the steady-state localisation and re-localisation of proteins. Here, we describe a principled Bayesian approach, BANDLE, that uses these data to compute the probability that a protein di erentially localises upon cellular perturbation. Extensive simula- tion studies demonstrate that BANDLE reduces the number of both type I and type II errors compared to existing approaches. Application of BANDLE to several datasets recovers well- studied translocations. In an application to cytomegalovirus infection, we obtain insights into the rewiring of the host proteome. Integration of other high-throughput datasets allows us to provide the functional context of these data.

Description

Keywords

Bayes Theorem, Mass Spectrometry, Proteome, Proteomics, Subcellular Fractions

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Nature Research
Sponsorship
Wellcome Trust (110170/Z/15/Z)
Wellcome Trust (110071/Z/15/Z)
Biotechnology and Biological Sciences Research Council (BB/N023129/1)