Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bridging topological and functional information in protein interaction networks by short loops profiling.

ABSTRACT: Protein-protein interaction networks (PPINs) have been employed to identify potential novel interconnections between proteins as well as crucial cellular functions. In this study we identify fundamental principles of PPIN topologies by analysing network motifs of short loops, which are small cyclic interactions of between 3 and 6 proteins. We compared 30 PPINs with corresponding randomised null models and examined the occurrence of common biological functions in loops extracted from a cross-validated high-confidence dataset of 622 human protein complexes. We demonstrate that loops are an intrinsic feature of PPINs and that specific cell functions are predominantly performed by loops of different lengths. Topologically, we find that loops are strongly related to the accuracy of PPINs and define a core of interactions with high resilience. The identification of this core and the analysis of loop composition are promising tools to assess PPIN quality and to uncover possible biases from experimental detection methods. More than 96% of loops share at least one biological function, with enrichment of cellular functions related to mRNA metabolic processing and the cell cycle. Our analyses suggest that these motifs can be used in the design of targeted experiments for functional phenotype detection.

SUBMITTER: Chung SS

PROVIDER: S-EPMC5224520 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Functional diversity of topological modules in human protein-protein interaction networks.

Project description:A large-scale molecular interaction network of protein-protein interactions (PPIs) enables the automatic detection of molecular functional modules through a computational approach. However, the functional modules that are typically detected by topological community detection algorithms may be diverse in functional homogeneity and are empirically considered to be default functional modules. Thus, a significant challenge that has been described but not elucidated is investigating the relationship between topological modules and functional modules. We systematically investigated this issue by initially using seven widely used community detection algorithms to partition the PPI network into communities. Four homogeneity measures were subsequently implemented to evaluate the functional homogeneity of protein community. We determined that a significant portion of topological modules with heterogeneous functionality exists and should be further investigated; moreover, these findings indicated that topologically based functional module detection approaches must be reconsidered. Furthermore, we found that the functional homogeneity of topological modules is positively correlated with their edge densities, degree of association with diseases and general Gene Ontology (GO) terms. Thus, topologically based module detection approaches should be used with caution in the identification of functional modules with high homogeneity.

| S-EPMC5701033 | biostudies-literature

Topological scoring of protein interaction networks.

Project description:It remains a significant challenge to define individual protein associations within networks where an individual protein can directly interact with other proteins and/or be part of large complexes, which contain functional modules. Here we demonstrate the topological scoring (TopS) algorithm for the analysis of quantitative proteomic datasets from affinity purifications. Data is analyzed in a parallel fashion where a prey protein is scored in an individual affinity purification by aggregating information from the entire dataset. Topological scores span a broad range of values indicating the enrichment of an individual protein in every bait protein purification. TopS is applied to interaction networks derived from human DNA repair proteins and yeast chromatin remodeling complexes. TopS highlights potential direct protein interactions and modules within complexes. TopS is a rapid method for the efficient and informative computational analysis of datasets, is complementary to existing analysis pipelines, and provides important insights into protein interaction networks.

| S-EPMC6408525 | biostudies-literature

Topological interaction by entangled DNA loops.

Project description:We have discovered a new type of interaction between micro- or nanoscale particles that results from the entanglement of strands attached to their surfaces. Self-complementary DNA single strands on a particle can hybridize to form loops. A similar proximal particle can have its loops catenate with those of the first. Unlike conventional thermodynamic interparticle interactions, the catenation interaction is strongly history and protocol dependent, allowing for nonequilibrium particle assembly. The interactions can be controlled by an interesting combination of forces, temperature, light sensitive cross-linking and enzymatic unwinding of the topological links. This novel topological interaction may lead to new materials and phenomena such as particles strung on necklaces, confined motions on designed contours and surfaces, and colloidal Olympic gels.

| S-EPMC3758925 | biostudies-literature

Functional characterization and topological modularity of molecular interaction networks.

Project description:BACKGROUND: Analyzing interaction networks for functional characterization poses significant challenges arising from the noisy, incomplete, and generic nature of both the interaction data as well as functional annotation of molecules. Network-based methods focus on interacting molecules (pairs or sets) occurring in close proximity to infer functional associations. RESULTS: In this paper we perform a formal comparative investigation of the relationship between functional coherence and topological proximity in networks. We investigate the problem of assessing the coherence of sets of biomolecules (or segments thereof) taking into account functional specificity as well as the distribution of functional attributes across entity groups. We also propose novel measures of topological proximity that are more robust to noisy and incomplete interaction data. CONCLUSION: We derive the following results in this paper: (i) there exists strong correlation between functional similarity and topological proximity in various network abstractions, with domain interaction networks (DDIs) demonstrating higher correlation than protein interaction networks (PPIs); (ii) measures that quantify coherence among entire sets of proteins are superior to aggregates of known pair-wise measures; and (iii) random-walk based measures of topological proximity are better suited to existing interaction data. We validate our methods on diverse data, including experimentally and computationally derived PPIs and DDIs, as well as on sets of known biologically related groups of molecules.

| S-EPMC3009507 | biostudies-literature

Association study based on topological constraints of protein-protein interaction networks.

Project description:The non-random interaction pattern of a protein-protein interaction network (PIN) is biologically informative, but its potentials have not been fully utilized in omics studies. Here, we propose a network-permutation-based association study (NetPAS) method that gauges the observed interactions between two sets of genes based on the comparison between permutation null models and the empirical networks. This enables NetPAS to evaluate relationships, constrained by network topology, between gene sets related to different phenotypes. We demonstrated the utility of NetPAS in 50 well-curated gene sets and comparison of association studies using Z-scores, modified Z'-scores, p-values and Jaccard indices. Using NetPAS, a weighted human disease network was generated from the association scores of 19 gene sets from OMIM. We also applied NetPAS in gene sets derived from gene ontology and pathway annotations and showed that NetPAS uncovered functional terms missed by DAVID and WebGestalt. Overall, we show that NetPAS can take topological constraints of molecular networks into account and offer new perspectives than existing methods.

| S-EPMC7329836 | biostudies-literature

Identification of Topological Network Modules in Perturbed Protein Interaction Networks.

Project description:Biological networks consist of functional modules, however detecting and characterizing such modules in networks remains challenging. Perturbing networks is one strategy for identifying modules. Here we used an advanced mathematical approach named topological data analysis (TDA) to interrogate two perturbed networks. In one, we disrupted the S. cerevisiae INO80 protein interaction network by isolating complexes after protein complex components were deleted from the genome. In the second, we reanalyzed previously published data demonstrating the disruption of the human Sin3 network with a histone deacetylase inhibitor. Here we show that disrupted networks contained topological network modules (TNMs) with shared properties that mapped onto distinct locations in networks. We define TMNs as proteins that occupy close network positions depending on their coordinates in a topological space. TNMs provide new insight into networks by capturing proteins from different categories including proteins within a complex, proteins with shared biological functions, and proteins disrupted across networks.

| S-EPMC5341041 | biostudies-literature

Simple topological features reflect dynamics and modularity in protein interaction networks.

Project description:The availability of large-scale protein-protein interaction networks for numerous organisms provides an opportunity to comprehensively analyze whether simple properties of proteins are predictive of the roles they play in the functional organization of the cell. We begin by re-examining an influential but controversial characterization of the dynamic modularity of the S. cerevisiae interactome that incorporated gene expression data into network analysis. We analyse the protein-protein interaction networks of five organisms, S. cerevisiae, H. sapiens, D. melanogaster, A. thaliana, and E. coli, and confirm significant and consistent functional and structural differences between hub proteins that are co-expressed with their interacting partners and those that are not, and support the view that the former tend to be intramodular whereas the latter tend to be intermodular. However, we also demonstrate that in each of these organisms, simple topological measures are significantly correlated with the average co-expression of a hub with its partners, independent of any classification, and therefore also reflect protein intra- and inter- modularity. Further, cross-interactomic analysis demonstrates that these simple topological characteristics of hub proteins tend to be conserved across organisms. Overall, we give evidence that purely topological features of static interaction networks reflect aspects of the dynamics and modularity of interactomes as well as previous measures incorporating expression data, and are a powerful means for understanding the dynamic roles of hubs in interactomes.

| S-EPMC3794914 | biostudies-literature

Conserved abundance and topological features in chromatin-remodeling protein interaction networks.

Project description:The study of conserved protein interaction networks seeks to better understand the evolution and regulation of protein interactions. Here, we present a quantitative proteomic analysis of 18 orthologous baits from three distinct chromatin-remodeling complexes in Saccharomyces cerevisiae and Homo sapiens. We demonstrate that abundance levels of orthologous proteins correlate strongly between the two organisms and both networks have highly similar topologies. We therefore used the protein abundances in one species to cross-predict missing protein abundance levels in the other species. Lastly, we identified a novel conserved low-abundance subnetwork further demonstrating the value of quantitative analysis of networks.

| S-EPMC4304735 | biostudies-literature

Comparative interaction networks: bridging genotype to phenotype.

Project description:Over the past decade, biomedical research has witnessed an exponential increase in the throughput of the characterization of biological systems. Here we review the recent progress in large-scale methods to determine protein-protein, genetic and chemical-genetic interaction networks. We discuss some of the limitations and advantages of the different methods and give examples of how these networks are being used to study the evolutionary process. Comparative studies have revealed that different types of protein-protein interactions diverge at different rates with high conservation of co-complex membership but rapid divergence of more promiscuous interactions like those that mediate post-translational modifications. These evolutionary trends have consistent genetic consequences with highly conserved epistatic interactions within complex subunits but faster divergence of epistatic interactions across complexes or pathways. Finally, we discuss how these evolutionary observations are being used to interpret cross-species chemical-genetic studies and how they might shape therapeutic strategies. Together, these interaction networks offer us an unprecedented level of detail into how genotypes are translated to phenotypes, and we envision that they will be increasingly useful in the interpretation of genetic and phenotypic variation occurring within populations as well as the rational design of combinatorial therapeutics.

| S-EPMC3518490 | biostudies-literature

A novel link prediction algorithm for reconstructing protein-protein interaction networks by topological similarity.

Project description:MotivationRecent advances in technology have dramatically increased the availability of protein-protein interaction (PPI) data and stimulated the development of many methods for improving the systems level understanding the cell. However, those efforts have been significantly hindered by the high level of noise, sparseness and highly skewed degree distribution of PPI networks. Here, we present a novel algorithm to reduce the noise present in PPI networks. The key idea of our algorithm is that two proteins sharing some higher-order topological similarities, measured by a novel random walk-based procedure, are likely interacting with each other and may belong to the same protein complex.ResultsApplying our algorithm to a yeast PPI network, we found that the edges in the reconstructed network have higher biological relevance than in the original network, assessed by multiple types of information, including gene ontology, gene expression, essentiality, conservation between species and known protein complexes. Comparison with existing methods shows that the network reconstructed by our method has the highest quality. Using two independent graph clustering algorithms, we found that the reconstructed network has resulted in significantly improved prediction accuracy of protein complexes. Furthermore, our method is applicable to PPI networks obtained with different experimental systems, such as affinity purification, yeast two-hybrid (Y2H) and protein-fragment complementation assay (PCA), and evidence shows that the predicted edges are likely bona fide physical interactions. Finally, an application to a human PPI network increased the coverage of the network by at least 100%.Availabilitywww.cs.utsa.edu/∼jruan/RWS/.

| S-EPMC3562060 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data