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BMC Research Notes

, 4:520

First Online: 28 November 2011Received: 30 December 2010Accepted: 28 November 2011DOI: 10.1186-1756-0500-4-520

Cite this article as: Ante, M., Wingender, E. & Fuchs, M. BMC Res Notes 2011 4: 520. doi:10.1186-1756-0500-4-520

Abstract

BackgroundReconstruction of protein-protein interaction or metabolic networks based on expression data often involves in silico predictions, while on the other hand, there are unspecific networks of in vivo interactions derived from knowledge bases.

We analyze networks designed to come as close as possible to data measured in vivo, both with respect to the set of nodes which were taken to be expressed in experiment as well as with respect to the interactions between them which were taken from manually curated databases

ResultsA signaling network derived from the TRANSPATH database and a metabolic network derived from KEGG LIGAND are each filtered onto expression data from breast cancer SAGE considering different levels of restrictiveness in edge and vertex selection.

We perform several validation steps, in particular we define pathway over-representation tests based on refined null models to recover functional modules. The prominent role of the spindle checkpoint-related pathways in breast cancer is exhibited. High-ranking key nodes cluster in functional groups retrieved from literature. Results are consistent between several functional and topological analyses and between signaling and metabolic aspects.

ConclusionsThis construction involved as a crucial step the passage to a mammalian protein identifier format as well as to a reaction-based semantics of metabolism. This yielded good connectivity but also led to the need to perform benchmark tests to exclude loss of essential information. Such validation, albeit tedious due to limitations of existing methods, turned out to be informative, and in particular provided biological insights as well as information on the degrees of coherence of the networks despite fragmentation of experimental data.

Key node analysis exploited the networks for potentially interesting proteins in view of drug target prediction.

Electronic supplementary materialThe online version of this article doi:10.1186-1756-0500-4-520 contains supplementary material, which is available to authorized users.

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Autor: Michael Ante - Edgar Wingender - Mathias Fuchs

Fuente: https://link.springer.com/







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