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. 2010 Jun 24;6(6):e1000807.
doi: 10.1371/journal.pcbi.1000807.

Protein-protein interactions essentials: key concepts to building and analyzing interactome networks

Javier De Las Rivas  1 , Celia Fontanillo
Affiliations

Protein-protein interactions essentials: key concepts to building and analyzing interactome networks

Javier De Las Rivas et al. PLoS Comput Biol. .
No abstract available

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Binary methods and co-complex methods: two approaches to determine PPIs.
The two most widely used experimental proteomic techniques applied to measure PPIs are yeast two-hybrid (Y2H) and tandem affinity purification coupled to mass spectrometry (TAP-MS); the former technique is a binary method (which measures physical direct interactions between protein pairs), and the latter a co-complex method (which measures physical interactions between groups of proteins without distinguishing whether they are direct or indirect). The interactions shown in the left panel (green links) correspond to the true interactions existing between two groups of proteins (set A with four proteins and set B with three proteins). The interactions shown in the right panels correspond to the networks derived from the experimentally measured interactions existing between the six proteins analyzed: the network in the top right panel (blue links) presents the interactions obtained using a binary method; the network in the bottom right panel (red links) presents the interactions obtained using a co-complex method. The red links are calculated applying the spoke model to the TAP-MS experimental data, but three of the interactions deduced (links with an X) do not occur.
Figure 2
Figure 2. Human interactome: overlap of six databases and coverage of 3-D structural data.
Analysis of human interactome PPI data showing the coverage of six major primary databases (BIND, BioGRID, DIP, HPRD, IntAct, and MINT), according to the integration provided by the meta-database APID. (A) Growth of the total number of human PPIs during the last 3 years. (B) Number of PPIs obtained from each primary repository showing the % (with respect to the total number of PPIs: 80,032 in December 2009) and the number of PPIs only reported by each database (shown inside the corresponding sector of the Venn diagram). Coverage and intersection of PPIs with 3-D structural information: (C) Intersection between the PPIs of all human proteins that have at least one Pfam annotated (69,079 interactions, called ppihs_all) and the PPIs that include proteins with 3-D structural information (9,879 interactions, called ppihsxsdd); (D) intersection between the PPIs with 3-D structural information and a more stringent interactome constituted by PPIs proven at least by two experimental methods (16,959 interactions, called ppihsx2meth); (E) intersection between the PPIs with 3-D structural information and more stringent interactome constituted by interactions between proteins that are annotated to the same KEGG functional pathway (7,693 interactions, called ppihsxKEGG).
Figure 3
Figure 3. A network derived from PPIs compared to the related canonical pathway.
Comparison between a known pathway (NOTCH signaling pathway, taken from the KEGG database, ID: hsa04330) and the corresponding interactome network build using the proteins that interact with human NOTCH proteins. The top panel (A) shows the pathway including nine proteins (green boxes) directly connected to NOTCH. In this pathway, the central element is the NOTCH receptor and the interaction of its intracellular domain (called NICD) with protein RBPJ. The bottom panel (B) shows the NOTCH PPI network (built with Cytoscape and APID2NET), including all interactors proven with at least two different experiments. The number of experiments is indicated next to each link (blue line). The PPI network provides complementry information to the KEGG pathway, revealing the particular links of each of the four NOTCH paralogous proteins (NOTCH1, 2, 3, and 4) present in the human proteome. The biomolecular elements included in both networks are quite similar and the information that can be deduced from them is complementary. This can be seen in the interaction between NOTCH and RBPJ that drives the central signaling of the pathway and it is present in both networks.
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