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Issue 10, 2011
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Enrichment and aggregation of topological motifs are independent organizational principles of integrated interaction networks

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Abstract

Topological network motifs represent functional relationships within and between regulatory and proteinprotein interaction networks. Enriched motifs often aggregate into self-contained units forming functional modules. Theoretical models for network evolution by duplication–divergence mechanisms and for network topology by hierarchical scale-free networks have suggested a one-to-one relation between network motif enrichment and aggregation, but this relation has never been tested quantitatively in real biological interaction networks. Here we introduce a novel method for assessing the statistical significance of network motif aggregation and for identifying clusters of overlapping network motifs. Using an integrated network of transcriptional, posttranslational and proteinprotein interactions in yeast we show that network motif aggregation reflects a local modularity property which is independent of network motif enrichment. In particular our method identified novel functional network themes for a set of motifs which are not enriched yet aggregate significantly and challenges the conventional view that network motif enrichment is the most basic organizational principle of complex networks.

Graphical abstract: Enrichment and aggregation of topological motifs are independent organizational principles of integrated interaction networks

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Supplementary files

Article information


Submitted
16 Jun 2011
Accepted
03 Aug 2011
First published
23 Aug 2011

Mol. BioSyst., 2011,7, 2769-2778
Article type
Paper

Enrichment and aggregation of topological motifs are independent organizational principles of integrated interaction networks

T. Michoel, A. Joshi, B. Nachtergaele and Y. Van de Peer, Mol. BioSyst., 2011, 7, 2769
DOI: 10.1039/C1MB05241A

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