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Characterization of known protein complexes using k-connectivity and other topological measures.

ABSTRACT: Many protein complexes are densely packed, so proteins within complexes often interact with several other proteins in the complex. Steric constraints prevent most proteins from simultaneously binding more than a handful of other proteins, regardless of the number of proteins in the complex. Because of this, as complex size increases, several measures of the complex decrease within protein-protein interaction networks. However, k-connectivity, the number of vertices or edges that need to be removed in order to disconnect a graph, may be consistently high for protein complexes. The property of k-connectivity has been little used previously in the investigation of protein-protein interactions. To understand the discriminative power of k-connectivity and other topological measures for identifying unknown protein complexes, we characterized these properties in known Saccharomyces cerevisiae protein complexes in networks generated both from highly accurate X-ray crystallography experiments which give an accurate model of each complex, and also as the complexes appear in high-throughput yeast 2-hybrid studies in which new complexes may be discovered. We also computed these properties for appropriate random subgraphs.We found that clustering coefficient, mutual clustering coefficient, and k-connectivity are better indicators of known protein complexes than edge density, degree, or betweenness. This suggests new directions for future protein complex-finding algorithms.

SUBMITTER: Gallagher SR

PROVIDER: S-EPMC4743144 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Characterization of known protein complexes using k-connectivity and other topological measures.

Gallagher Suzanne R SR Goldberg Debra S DS

F1000Research 20130813

Many protein complexes are densely packed, so proteins within complexes often interact with several other proteins in the complex. Steric constraints prevent most proteins from simultaneously binding more than a handful of other proteins, regardless of the number of proteins in the complex. Because of this, as complex size increases, several measures of the complex decrease within protein-protein interaction networks. However, k-connectivity, the number of vertices or edges that need to be remov ...[more]

PMID: 26913183

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Project description:IntroductionStructural MRI has long been used to characterize local morphological features of the human brain. Coordination patterns of the local morphological features among regions, however, are not well understood. Here, we constructed individual-level morphological brain networks and systematically examined their topological organization and long-term test-retest reliability under different analytical schemes of spatial smoothing, brain parcellation, and network type.MethodsThis study included 57 healthy participants and all participants completed two MRI scan sessions. Individual morphological brain networks were constructed by estimating interregional similarity in the distribution of regional gray matter volume in terms of the Kullback-Leibler divergence measure. Graph-based global and nodal network measures were then calculated, followed by the statistical comparison and intra-class correlation analysis.ResultsThe morphological brain networks were highly reproducible between sessions with significantly larger similarities for interhemispheric connections linking bilaterally homotopic regions. Further graph-based analyses revealed that the morphological brain networks exhibited nonrandom topological organization of small-worldness, high parallel efficiency and modular architecture regardless of the analytical choices of spatial smoothing, brain parcellation and network type. Moreover, several paralimbic and association regions were consistently revealed to be potential hubs. Nonetheless, the three studied factors particularly spatial smoothing significantly affected quantitative characterization of morphological brain networks. Further examination of long-term reliability revealed that all the examined network topological properties showed fair to excellent reliability irrespective of the analytical strategies, but performing spatial smoothing significantly improved reliability. Interestingly, nodal centralities were positively correlated with their reliabilities, and nodal degree and efficiency outperformed nodal betweenness with respect to reliability.ConclusionsOur findings support single-subject morphological network analysis as a meaningful and reliable method to characterize structural organization of the human brain; this method thus opens a new avenue toward understanding the substrate of intersubject variability in behavior and function and establishing morphological network biomarkers in brain disorders.

Dataset Information

Characterization of known protein complexes using k-connectivity and other topological measures.

Publications

Characterization of known protein complexes using k-connectivity and other topological measures.

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