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BY-NC-ND 4.0 license Open Access Published by De Gruyter October 18, 2016

Integrating Protein-Protein Interaction Networks with Gene- Gene Co-Expression Networks improves Gene Signatures for Classifying Breast Cancer Metastasis

  • Erik van den Akker EMAIL logo , Bas Verbruggen , Bas Heijmans , Marian Beekman , Joost Kok , Eline Slagboom and Marcel Reinders


Multiple studies have illustrated that gene expression profiling of primary breast cancers throughout the final stages of tumor development can provide valuable markers for risk prediction of metastasis and disease sub typing. However, the identification of a biologically interpretable and universally shared set of markers proved to be difficult. Here, we propose a method for de novo grouping of genes by dissecting the proteinprotein interaction network into disjoint sub networks using pair wise gene expression correlation measures. We show that the obtained sub networks are functionally coherent and are consistently identified when applied on a compendium composed of six different breast cancer studies. Application of the proposed method using different integration approaches underlines the robustness of the identified sub network related to cell cycle and identifies putative new sub network markers for metastasis related to cell-cell adhesion, the proteasome complex and JUN-FOS signalling. Although gene selection with the proposed method does not directly improve upon previously reported cross study classification performances, it shows great promises for applications in data integration and result interpretation.

Published Online: 2016-10-18
Published in Print: 2011-6-1

© 2011 The Author(s). Published by Journal of Integrative Bioinformatics.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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