Extending pathways and processes using molecular interaction networks to analyse cancer genome data

BACKGROUND: Cellular processes and pathways, whose deregulation may contribute to the development of cancers, are often represented as cascades of proteins transmitting a signal from the cell surface to the nucleus. However, recent functional genomic experiments have identified thousands of interact...

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Main Authors: Glaab, Enrico, Baudot, Anaïs, Krasnogor, Natalio, Valencia, Alfonso
Format: Article
Published: BioMed Central Ltd 2010
Online Access:https://eprints.nottingham.ac.uk/1421/
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author Glaab, Enrico
Baudot, Anaïs
Krasnogor, Natalio
Valencia, Alfonso
author_facet Glaab, Enrico
Baudot, Anaïs
Krasnogor, Natalio
Valencia, Alfonso
author_sort Glaab, Enrico
building Nottingham Research Data Repository
collection Online Access
description BACKGROUND: Cellular processes and pathways, whose deregulation may contribute to the development of cancers, are often represented as cascades of proteins transmitting a signal from the cell surface to the nucleus. However, recent functional genomic experiments have identified thousands of interactions for the signalling canonical proteins, challenging the traditional view of pathways as independent functional entities. Combining information from pathway databases and interaction networks obtained from functional genomic experiments is therefore a promising strategy to obtain more robust pathway and process representations, facilitating the study of cancer-related pathways. RESULTS: We present a methodology for extending pre-defined protein sets representing cellular pathways and processes by mapping them onto a protein-protein interaction network, and extending them to include densely interconnected interaction partners. The added proteins display distinctive network topological features and molecular function annotations, and can be proposed as putative new components, and/or as regulators of the communication between the different cellular processes. Finally, these extended pathways and processes are used to analyse their enrichment in pancreatic mutated genes. Significant associations between mutated genes and certain processes are identified, enabling an analysis of the influence of previously non-annotated cancer mutated genes. CONCLUSIONS: The proposed method for extending cellular pathways helps to explain the functions of cancer mutated genes by exploiting the synergies of canonical knowledge and large-scale interaction data.
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spelling nottingham-14212020-05-04T16:30:06Z https://eprints.nottingham.ac.uk/1421/ Extending pathways and processes using molecular interaction networks to analyse cancer genome data Glaab, Enrico Baudot, Anaïs Krasnogor, Natalio Valencia, Alfonso BACKGROUND: Cellular processes and pathways, whose deregulation may contribute to the development of cancers, are often represented as cascades of proteins transmitting a signal from the cell surface to the nucleus. However, recent functional genomic experiments have identified thousands of interactions for the signalling canonical proteins, challenging the traditional view of pathways as independent functional entities. Combining information from pathway databases and interaction networks obtained from functional genomic experiments is therefore a promising strategy to obtain more robust pathway and process representations, facilitating the study of cancer-related pathways. RESULTS: We present a methodology for extending pre-defined protein sets representing cellular pathways and processes by mapping them onto a protein-protein interaction network, and extending them to include densely interconnected interaction partners. The added proteins display distinctive network topological features and molecular function annotations, and can be proposed as putative new components, and/or as regulators of the communication between the different cellular processes. Finally, these extended pathways and processes are used to analyse their enrichment in pancreatic mutated genes. Significant associations between mutated genes and certain processes are identified, enabling an analysis of the influence of previously non-annotated cancer mutated genes. CONCLUSIONS: The proposed method for extending cellular pathways helps to explain the functions of cancer mutated genes by exploiting the synergies of canonical knowledge and large-scale interaction data. BioMed Central Ltd 2010-12-13 Article PeerReviewed Glaab, Enrico, Baudot, Anaïs, Krasnogor, Natalio and Valencia, Alfonso (2010) Extending pathways and processes using molecular interaction networks to analyse cancer genome data. BMC Bioinformatics, 11 (597). pp. 1-11. ISSN 1471-2105 http://www.biomedcentral.com/1471-2105/11/597
spellingShingle Glaab, Enrico
Baudot, Anaïs
Krasnogor, Natalio
Valencia, Alfonso
Extending pathways and processes using molecular interaction networks to analyse cancer genome data
title Extending pathways and processes using molecular interaction networks to analyse cancer genome data
title_full Extending pathways and processes using molecular interaction networks to analyse cancer genome data
title_fullStr Extending pathways and processes using molecular interaction networks to analyse cancer genome data
title_full_unstemmed Extending pathways and processes using molecular interaction networks to analyse cancer genome data
title_short Extending pathways and processes using molecular interaction networks to analyse cancer genome data
title_sort extending pathways and processes using molecular interaction networks to analyse cancer genome data
url https://eprints.nottingham.ac.uk/1421/
https://eprints.nottingham.ac.uk/1421/