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Organization of physical interactomes as uncovered by network schemas.

Banks E, Nabieva E, Chazelle B, Singh M - PLoS Comput. Biol. (2008)

Bottom Line: We apply our methods to the S. cerevisiae interactome, focusing on schemas consisting of proteins described via sequence motifs and molecular function annotations and interacting with one another in one of four basic network topologies.We identify hundreds of recurring and over-represented network schemas of various complexity, and demonstrate via graph-theoretic representations how more complex schemas are organized in terms of their lower-order constituents.We establish the functional importance of the schemas by showing that they correspond to functionally cohesive sets of proteins, are enriched in the frequency with which they have instances in the H. sapiens interactome, and are useful for predicting protein function.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science & Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.

ABSTRACT
Large-scale protein-protein interaction networks provide new opportunities for understanding cellular organization and functioning. We introduce network schemas to elucidate shared mechanisms within interactomes. Network schemas specify descriptions of proteins and the topology of interactions among them. We develop algorithms for systematically uncovering recurring, over-represented schemas in physical interaction networks. We apply our methods to the S. cerevisiae interactome, focusing on schemas consisting of proteins described via sequence motifs and molecular function annotations and interacting with one another in one of four basic network topologies. We identify hundreds of recurring and over-represented network schemas of various complexity, and demonstrate via graph-theoretic representations how more complex schemas are organized in terms of their lower-order constituents. The uncovered schemas span a wide range of cellular activities, with many signaling and transport related higher-order schemas. We establish the functional importance of the schemas by showing that they correspond to functionally cohesive sets of proteins, are enriched in the frequency with which they have instances in the H. sapiens interactome, and are useful for predicting protein function. Our findings suggest that network schemas are a powerful paradigm for organizing, interrogating, and annotating cellular networks.

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Pfam pair schemas that are found in both H. sapiens and S. cerevisiae.Schemas that are emergent in both organisms are displayed with red edges. Schemas that are emergent only in H. sapiens but that have instances in S. cerevisiae are shown with light blue edges. Schemas that are emergent only in S. cerevisiae but that have instances in H. sapiens are indicated with grey edges.
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pcbi-1000203-g005: Pfam pair schemas that are found in both H. sapiens and S. cerevisiae.Schemas that are emergent in both organisms are displayed with red edges. Schemas that are emergent only in H. sapiens but that have instances in S. cerevisiae are shown with light blue edges. Schemas that are emergent only in S. cerevisiae but that have instances in H. sapiens are indicated with grey edges.

Mentions: To compare the types of schemas that are emergent across distant genomes, we uncover pair schemas in the H. sapiens interactome (Figures 5 and 6 and Table S7). We identify 29 pair schemas that are emergent schemas in both the S. cerevisiae and H. sapiens networks, as well as several that are emergent schemas only in H. sapiens but have instances in S. cerevisiae (Figure 5). As expected, these schemas represent some of the most basic processes that occur within the cell: DNA packaging, cytoskeleton organization, signaling, vesicle fusion, and so on.


Organization of physical interactomes as uncovered by network schemas.

Banks E, Nabieva E, Chazelle B, Singh M - PLoS Comput. Biol. (2008)

Pfam pair schemas that are found in both H. sapiens and S. cerevisiae.Schemas that are emergent in both organisms are displayed with red edges. Schemas that are emergent only in H. sapiens but that have instances in S. cerevisiae are shown with light blue edges. Schemas that are emergent only in S. cerevisiae but that have instances in H. sapiens are indicated with grey edges.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2561054&req=5

pcbi-1000203-g005: Pfam pair schemas that are found in both H. sapiens and S. cerevisiae.Schemas that are emergent in both organisms are displayed with red edges. Schemas that are emergent only in H. sapiens but that have instances in S. cerevisiae are shown with light blue edges. Schemas that are emergent only in S. cerevisiae but that have instances in H. sapiens are indicated with grey edges.
Mentions: To compare the types of schemas that are emergent across distant genomes, we uncover pair schemas in the H. sapiens interactome (Figures 5 and 6 and Table S7). We identify 29 pair schemas that are emergent schemas in both the S. cerevisiae and H. sapiens networks, as well as several that are emergent schemas only in H. sapiens but have instances in S. cerevisiae (Figure 5). As expected, these schemas represent some of the most basic processes that occur within the cell: DNA packaging, cytoskeleton organization, signaling, vesicle fusion, and so on.

Bottom Line: We apply our methods to the S. cerevisiae interactome, focusing on schemas consisting of proteins described via sequence motifs and molecular function annotations and interacting with one another in one of four basic network topologies.We identify hundreds of recurring and over-represented network schemas of various complexity, and demonstrate via graph-theoretic representations how more complex schemas are organized in terms of their lower-order constituents.We establish the functional importance of the schemas by showing that they correspond to functionally cohesive sets of proteins, are enriched in the frequency with which they have instances in the H. sapiens interactome, and are useful for predicting protein function.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science & Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.

ABSTRACT
Large-scale protein-protein interaction networks provide new opportunities for understanding cellular organization and functioning. We introduce network schemas to elucidate shared mechanisms within interactomes. Network schemas specify descriptions of proteins and the topology of interactions among them. We develop algorithms for systematically uncovering recurring, over-represented schemas in physical interaction networks. We apply our methods to the S. cerevisiae interactome, focusing on schemas consisting of proteins described via sequence motifs and molecular function annotations and interacting with one another in one of four basic network topologies. We identify hundreds of recurring and over-represented network schemas of various complexity, and demonstrate via graph-theoretic representations how more complex schemas are organized in terms of their lower-order constituents. The uncovered schemas span a wide range of cellular activities, with many signaling and transport related higher-order schemas. We establish the functional importance of the schemas by showing that they correspond to functionally cohesive sets of proteins, are enriched in the frequency with which they have instances in the H. sapiens interactome, and are useful for predicting protein function. Our findings suggest that network schemas are a powerful paradigm for organizing, interrogating, and annotating cellular networks.

Show MeSH