Reconstruction of the experimentally supported human protein interactome: what can we learn?

Background Understanding the topology and dynamics of the human protein-protein interaction (PPI) network will significantly contribute to biomedical research, therefore its systematic reconstruction is required. Several meta-databases integrate source PPI datasets, but the protein node sets of thei...
Ausführliche Beschreibung

Background Understanding the topology and dynamics of the human protein-protein interaction (PPI) network will significantly contribute to biomedical research, therefore its systematic reconstruction is required. Several meta-databases integrate source PPI datasets, but the protein node sets of their networks vary depending on the PPI data combined. Due to this inherent heterogeneity, the way in which the human PPI network expands via multiple dataset integration has not been comprehensively analyzed. We aim at assembling the human interactome in a global structured way and exploring it to gain insights of biological relevance. Results First, we defined the UniProtKB manually reviewed human “complete” proteome as the reference protein-node set and then we mined five major source PPI datasets for direct PPIs exclusively between the reference proteins. We updated the protein and publication identifiers and normalized all PPIs to the UniProt identifier level. The reconstructed interactome covers approximately 60% of the human proteome and has a scale-free structure. No apparent differentiating gene functional classification characteristics were identified for the unrepresented proteins. The source dataset integration augments the network mainly in PPIs. Polyubiquitin emerged as the highest-degree node, but the inclusion of most of its identified PPIs may be reconsidered. The high number (>300) of connections of the subsequent fifteen proteins correlates well with their essential biological role. According to the power-law network structure, the unrepresented proteins should mainly have up to four connections with equally poorly-connected interactors. Conclusions Reconstructing the human interactome based on the a priori definition of the protein nodes enabled us to identify the currently included part of the human “complete” proteome, and discuss the role of the proteins within the network topology with respect to their function. As the network expansion has to comply with the scale-free theory, we suggest that the core of the human interactome has essentially emerged. Thus, it could be employed in systems biology and biomedical research, despite the considerable number of currently unrepresented proteins. The latter are probably involved in specialized physiological conditions, justifying the scarcity of related PPI information, and their identification can assist in designing relevant functional experiments and targeted text mining algorithms. Ausführliche Beschreibung

Autor*in:	Klapa, Maria I [verfasserIn] Tsafou, Kalliopi Theodoridis, Evangelos Tsakalidis, Athanasios Moschonas, Nicholas K

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2013

Schlagwörter:	Human protein interactome analysis Human protein-protein interaction (PPI) databases Network biology PPI network reconstruction

Anmerkung:	© Klapa et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: BMC systems biology - London : BioMed Central, 2007, 7(2013), 1 vom: 02. Okt.
Übergeordnetes Werk:	volume:7 ; year:2013 ; number:1 ; day:02 ; month:10

Links:	Volltext

DOI / URN:	10.1186/1752-0509-7-96

Katalog-ID:	SPR028415868