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Learning from Heterogeneous Data Sources: An Application in Spatial Proteomics.

Published version
Peer-reviewed

Repository DOI


Change log

Authors

Breckels, Lisa M 
Holden, Sean B 
Wojnar, David 
Mulvey, Claire M 
Christoforou, Andy 

Abstract

Sub-cellular localisation of proteins is an essential post-translational regulatory mechanism that can be assayed using high-throughput mass spectrometry (MS). These MS-based spatial proteomics experiments enable us to pinpoint the sub-cellular distribution of thousands of proteins in a specific system under controlled conditions. Recent advances in high-throughput MS methods have yielded a plethora of experimental spatial proteomics data for the cell biology community. Yet, there are many third-party data sources, such as immunofluorescence microscopy or protein annotations and sequences, which represent a rich and vast source of complementary information. We present a unique transfer learning classification framework that utilises a nearest-neighbour or support vector machine system, to integrate heterogeneous data sources to considerably improve on the quantity and quality of sub-cellular protein assignment. We demonstrate the utility of our algorithms through evaluation of five experimental datasets, from four different species in conjunction with four different auxiliary data sources to classify proteins to tens of sub-cellular compartments with high generalisation accuracy. We further apply the method to an experiment on pluripotent mouse embryonic stem cells to classify a set of previously unknown proteins, and validate our findings against a recent high resolution map of the mouse stem cell proteome. The methodology is distributed as part of the open-source Bioconductor pRoloc suite for spatial proteomics data analysis.

Description

Keywords

Algorithms, Animals, Arabidopsis, Computational Biology, Data Interpretation, Statistical, Drosophila, Embryonic Stem Cells, Humans, Information Storage and Retrieval, Mass Spectrometry, Mice, Proteome, Proteomics, Software, Subcellular Fractions, Support Vector Machine

Journal Title

PLoS Comput Biol

Conference Name

Journal ISSN

1553-734X
1553-7358

Volume Title

12

Publisher

Public Library of Science (PLoS)
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/K00137X/1)
Wellcome Trust (108441/Z/15/Z)
European Commission (262067)
Biotechnology and Biological Sciences Research Council (BB/L002817/1)
LMB was supported by a BBSRC Tools and Resources Development Fund (Award BB/K00137X/1) and a Wellcome Trust Technology Development Grant (108441/Z/15/Z). LG was supported by the European Union 7th Framework Program (PRIME-XS project, grant agreement number 262067) and a BBSRC Strategic Longer and Larger Award (Award BB/L002817/1). DW and OK acknowledge funding from the European Union (PRIME-XS, GA 262067) and Deutsche Forschungsgemeinschaft (KO-2313/6-1).