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Functional integrative levels in the human interactome recapitulate organ organization.

Souiai O, Becker E, Prieto C, Benkahla A, De las Rivas J, Brun C - PLoS ONE (2011)

Bottom Line: Overall, the functional organization of the human interactome reflects several integrative levels of functions with housekeeping and regulatory tissue-specific functions at the center and physiological tissue-specific functions at the periphery.This gradient of functions recapitulates the organization of organs, from cells to organs.Given that several gradients have already been identified across interactomes, we propose that gradients may represent a general principle of protein-protein interaction network organization.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U928, TAGC, Marseille, France.

ABSTRACT
Interactome networks represent sets of possible physical interactions between proteins. They lack spatio-temporal information by construction. However, the specialized functions of the differentiated cell types which are assembled into tissues or organs depend on the combinatorial arrangements of proteins and their physical interactions. Is tissue-specificity, therefore, encoded within the interactome? In order to address this question, we combined protein-protein interactions, expression data, functional annotations and interactome topology. We first identified a subnetwork formed exclusively of proteins whose interactions were observed in all tested tissues. These are mainly involved in housekeeping functions and are located at the topological center of the interactome. This 'Largest Common Interactome Network' represents a 'functional interactome core'. Interestingly, two types of tissue-specific interactions are distinguished when considering function and network topology: tissue-specific interactions involved in regulatory and developmental functions are central whereas tissue-specific interactions involved in organ physiological functions are peripheral. Overall, the functional organization of the human interactome reflects several integrative levels of functions with housekeeping and regulatory tissue-specific functions at the center and physiological tissue-specific functions at the periphery. This gradient of functions recapitulates the organization of organs, from cells to organs. Given that several gradients have already been identified across interactomes, we propose that gradients may represent a general principle of protein-protein interaction network organization.

Show MeSH
Distribution of the interaction usage in the human interactome.Bins correspond to the number of tissues in which interactions are possible.
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pone-0022051-g002: Distribution of the interaction usage in the human interactome.Bins correspond to the number of tissues in which interactions are possible.

Mentions: To reflect this difference, we defined the notion of ‘interaction usage’ (IU) as the number of tissues in which an interaction is possible. This corresponds to the number of tissues in which both interactors are co-expressed (Table S1). The distribution of the IU values (Figure 2) shows first, the scarcity of strictly tissue-specific interactions: only 5% of the interactions are possible in less than 3 tissues and 11% in less than 6 tissues; second, that 77% of the interactions are possible in more than half of the tissues; and third, that 21% of the interactions are common to all the considered tissues.


Functional integrative levels in the human interactome recapitulate organ organization.

Souiai O, Becker E, Prieto C, Benkahla A, De las Rivas J, Brun C - PLoS ONE (2011)

Distribution of the interaction usage in the human interactome.Bins correspond to the number of tissues in which interactions are possible.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140469&req=5

pone-0022051-g002: Distribution of the interaction usage in the human interactome.Bins correspond to the number of tissues in which interactions are possible.
Mentions: To reflect this difference, we defined the notion of ‘interaction usage’ (IU) as the number of tissues in which an interaction is possible. This corresponds to the number of tissues in which both interactors are co-expressed (Table S1). The distribution of the IU values (Figure 2) shows first, the scarcity of strictly tissue-specific interactions: only 5% of the interactions are possible in less than 3 tissues and 11% in less than 6 tissues; second, that 77% of the interactions are possible in more than half of the tissues; and third, that 21% of the interactions are common to all the considered tissues.

Bottom Line: Overall, the functional organization of the human interactome reflects several integrative levels of functions with housekeeping and regulatory tissue-specific functions at the center and physiological tissue-specific functions at the periphery.This gradient of functions recapitulates the organization of organs, from cells to organs.Given that several gradients have already been identified across interactomes, we propose that gradients may represent a general principle of protein-protein interaction network organization.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U928, TAGC, Marseille, France.

ABSTRACT
Interactome networks represent sets of possible physical interactions between proteins. They lack spatio-temporal information by construction. However, the specialized functions of the differentiated cell types which are assembled into tissues or organs depend on the combinatorial arrangements of proteins and their physical interactions. Is tissue-specificity, therefore, encoded within the interactome? In order to address this question, we combined protein-protein interactions, expression data, functional annotations and interactome topology. We first identified a subnetwork formed exclusively of proteins whose interactions were observed in all tested tissues. These are mainly involved in housekeeping functions and are located at the topological center of the interactome. This 'Largest Common Interactome Network' represents a 'functional interactome core'. Interestingly, two types of tissue-specific interactions are distinguished when considering function and network topology: tissue-specific interactions involved in regulatory and developmental functions are central whereas tissue-specific interactions involved in organ physiological functions are peripheral. Overall, the functional organization of the human interactome reflects several integrative levels of functions with housekeeping and regulatory tissue-specific functions at the center and physiological tissue-specific functions at the periphery. This gradient of functions recapitulates the organization of organs, from cells to organs. Given that several gradients have already been identified across interactomes, we propose that gradients may represent a general principle of protein-protein interaction network organization.

Show MeSH