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. 2015 Jun 15;8(6):9384-93.
eCollection 2015.

Systematic tracking of dysregulated modules identifies disrupted pathways in narcolepsy

Zhenhua Liu  1 , Jiali Zhao  2 , Yinyin Tan  2 , Minglu Tang  3 , Guanzhen Li  3
Affiliations

Systematic tracking of dysregulated modules identifies disrupted pathways in narcolepsy

Zhenhua Liu et al. Int J Clin Exp Med. .

Abstract

Objective: The objective of this work is to identify disrupted pathways in narcolepsy according to systematically tracking the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. Here, we performed systematic identification and comparison of modules across normal and narcolepsy conditions by integrating PPI and gene-expression data.

Methods: Firstly, normal and narcolepsy PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, modules in PPI network were explored by clique-merging algorithm and we identified altered modules using a maximum weight bipartite matching and in non-increasing order. Finally, pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test to illuminate the biological pathways in narcolepsy.

Results: Our analyses revealed that 235 altered modules were identified by comparing modules in normal and narcolepsy PPI network. Pathway functional enrichment analysis of disrupted module genes showed 59 disrupted pathways within threshold P < 0.001. The most significant five disrupted pathways were: oxidative phosphorylation, T cell receptor signaling pathway, cell cycle, Alzheimer's disease and focal adhesion.

Conclusions: We successfully identified disrupted pathways and these pathways might be potential biological processes for treatment and etiology mechanism in narcolepsy.

Keywords: Narcolepsy; disrupted pathways; dysregulated modules; protein-protein interaction network.

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Figures

Figure 1
Figure 1
Scorewise distribution of interactions: Normal vs Narcolepsy.
Figure 2
Figure 2
Correlationwise distribution of modules in normal and narcolepsy. Expression correlation of one module was equaled to weighted interaction density in the module.
See this image and copyright information in PMC

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