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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.

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Largest Common Interactome Network analyses.(A) The sets of the most enriched (p-val<10−5) Biological Process (BP) annotations in the LCIN, visualized using SimCT [28] (http://tagc.univ-mrs.fr/SimCT/), a tool to visualize relationships between biological objects annotated to an ontology. (B) The sets of the most depleted (p-val<10−5) Biological Process (BP) annotations in the LCIN. (C) Distribution of interactions involving disease genes (according to OMIM) across the IU bins. (D) The LCIN is enriched in distant orthologues. Percentages of orthologs above the expected value (27%) are shown in orange. Enrichment p-values are given per organism.
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pone-0022051-g003: Largest Common Interactome Network analyses.(A) The sets of the most enriched (p-val<10−5) Biological Process (BP) annotations in the LCIN, visualized using SimCT [28] (http://tagc.univ-mrs.fr/SimCT/), a tool to visualize relationships between biological objects annotated to an ontology. (B) The sets of the most depleted (p-val<10−5) Biological Process (BP) annotations in the LCIN. (C) Distribution of interactions involving disease genes (according to OMIM) across the IU bins. (D) The LCIN is enriched in distant orthologues. Percentages of orthologs above the expected value (27%) are shown in orange. Enrichment p-values are given per organism.

Mentions: Interactions of the LCIN are expected to participate in housekeeping cellular functions which occur in all cell types. Indeed, GO term analysis shows that the LCIN is particularly enriched (p-val<10−5) in proteins involved in nucleic acid and protein metabolic processes, intracellular transport, and cellular processes linked to cell cycle and nuclear organization. Conversely, interactions involved in organ morphogenesis, systems development and establishment (such as the nervous or immunological systems) or cell communication are particularly under-represented (p-val<10−5) in the LCIN (Figure 3A, 3B; Table S4). We believe, therefore, that the LCIN represents a functional interactome core devoted to housekeeping functions.


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)

Largest Common Interactome Network analyses.(A) The sets of the most enriched (p-val<10−5) Biological Process (BP) annotations in the LCIN, visualized using SimCT [28] (http://tagc.univ-mrs.fr/SimCT/), a tool to visualize relationships between biological objects annotated to an ontology. (B) The sets of the most depleted (p-val<10−5) Biological Process (BP) annotations in the LCIN. (C) Distribution of interactions involving disease genes (according to OMIM) across the IU bins. (D) The LCIN is enriched in distant orthologues. Percentages of orthologs above the expected value (27%) are shown in orange. Enrichment p-values are given per organism.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0022051-g003: Largest Common Interactome Network analyses.(A) The sets of the most enriched (p-val<10−5) Biological Process (BP) annotations in the LCIN, visualized using SimCT [28] (http://tagc.univ-mrs.fr/SimCT/), a tool to visualize relationships between biological objects annotated to an ontology. (B) The sets of the most depleted (p-val<10−5) Biological Process (BP) annotations in the LCIN. (C) Distribution of interactions involving disease genes (according to OMIM) across the IU bins. (D) The LCIN is enriched in distant orthologues. Percentages of orthologs above the expected value (27%) are shown in orange. Enrichment p-values are given per organism.
Mentions: Interactions of the LCIN are expected to participate in housekeeping cellular functions which occur in all cell types. Indeed, GO term analysis shows that the LCIN is particularly enriched (p-val<10−5) in proteins involved in nucleic acid and protein metabolic processes, intracellular transport, and cellular processes linked to cell cycle and nuclear organization. Conversely, interactions involved in organ morphogenesis, systems development and establishment (such as the nervous or immunological systems) or cell communication are particularly under-represented (p-val<10−5) in the LCIN (Figure 3A, 3B; Table S4). We believe, therefore, that the LCIN represents a functional interactome core devoted to housekeeping functions.

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