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PathwayMatcher: proteoform-centric network construction enables fine-granularity multi-omics pathway mapping

Luis Francisco Hernández Sánchez, Bram Burger, Carlos Horro, Antonio Fabregat, Stefan Johansson, Pål Rasmus Njølstad, Harald Barsnes, Henning Hermjakob, Marc Vaudel
doi: https://doi.org/10.1101/375097
Luis Francisco Hernández Sánchez
1K.G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Norway
2Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
3European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
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Bram Burger
4Proteomics Unit, Department of Biomedicine, University of Bergen, Bergen, Norway
5Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway
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Carlos Horro
4Proteomics Unit, Department of Biomedicine, University of Bergen, Bergen, Norway
5Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway
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Antonio Fabregat
3European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
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Stefan Johansson
1K.G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Norway
2Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
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Pål Rasmus Njølstad
1K.G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Norway
6Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
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Harald Barsnes
4Proteomics Unit, Department of Biomedicine, University of Bergen, Bergen, Norway
5Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway
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Henning Hermjakob
3European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
7Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing, China
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Marc Vaudel
1K.G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Norway
2Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
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  • For correspondence: marc.vaudel@uib.no
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Abstract

Background Mapping biomedical data to functional knowledge is an essential task in bioinformatics and can be achieved by querying identifiers, e.g. gene sets, in pathway knowledgebases. However, the isoform and post-translational modification states of proteins are lost when converting input and pathways into gene-centric lists.

Findings Based on the Reactome knowledgebase, we built a network of protein-protein interactions accounting for the documented isoform and modification statuses of proteins. We then implemented a command line application called PathwayMatcher (github.com/PathwayAnalysisPlatform/PathwayMatcher) to query this network. PathwayMatcher supports multiple types of omics data as input, and outputs the possibly affected biochemical reactions, subnetworks, and pathways.

Conclusions PathwayMatcher enables refining the network-representation of pathways by including isoform and post-translational modifications. The specificity of pathway analyses is hence adapted to different levels of granularity and it becomes possible to distinguish interactions between different forms of the same protein.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 18, 2018.
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PathwayMatcher: proteoform-centric network construction enables fine-granularity multi-omics pathway mapping
Luis Francisco Hernández Sánchez, Bram Burger, Carlos Horro, Antonio Fabregat, Stefan Johansson, Pål Rasmus Njølstad, Harald Barsnes, Henning Hermjakob, Marc Vaudel
bioRxiv 375097; doi: https://doi.org/10.1101/375097
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PathwayMatcher: proteoform-centric network construction enables fine-granularity multi-omics pathway mapping
Luis Francisco Hernández Sánchez, Bram Burger, Carlos Horro, Antonio Fabregat, Stefan Johansson, Pål Rasmus Njølstad, Harald Barsnes, Henning Hermjakob, Marc Vaudel
bioRxiv 375097; doi: https://doi.org/10.1101/375097

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