Interaction network

About: Interaction network is a research topic. Over the lifetime, 2700 publications have been published within this topic receiving 113372 citations.

Evolutionary Rate and Duplicability in the Arabidopsis thaliana Protein–Protein Interaction Network

Abstract: Genes show a bewildering variation in their patterns of molecular evolution, as a result of the action of different levels and types of selective forces. The factors underlying this variation are, however, still poorly understood. In the last decade, the position of proteins in the protein–protein interaction network has been put forward as a determinant factor of the evolutionary rate and duplicability of their encoding genes. This conclusion, however, has been based on the analysis of the limited number of microbes and animals for which interactome-level data are available (essentially, Escherichia coli, yeast, worm, fly, and humans). Here, we study, for the first time, the relationship between the position of proteins in the high-density interactome of a plant (Arabidopsis thaliana) and the patterns of molecular evolution of their encoding genes. We found that genes whose encoded products act at the center of the network are more evolutionarily constrained than those acting at the network periphery. This trend remains significant when potential confounding factors (gene expression level and breadth, duplicability, function, and length of the encoded products) are controlled for. Even though the correlation between centrality measures and rates of evolution is generally weak, for some functional categories, it is comparable in strength to (or even stronger than) the correlation between evolutionary rates and expression levels or breadths. In addition, genes encoding interacting proteins in the network evolve at relatively similar rates. Finally, Arabidopsis proteins encoded by duplicated genes are more highly connected than those encoded by singleton genes. This observation is in agreement with the patterns observed in humans, but in contrast with those observed in E. coli, yeast, worm, and fly (whose duplicated genes tend to act at the periphery of the network), implying that the relationship between duplicability and centrality inverted at least twice during eukaryote evolution. Taken together, these results indicate that the structure of the A. thaliana network constrains the evolution of its components at multiple levels.

Comparative analysis of the Saccharomyces cerevisiae and Caenorhabditis elegans protein interaction networks

Abstract: Protein interaction networks aim to summarize the complex interplay of proteins in an organism. Early studies suggested that the position of a protein in the network determines its evolutionary rate but there has been considerable disagreement as to what extent other factors, such as protein abundance, modify this reported dependence. We compare the genomes of Saccharomyces cerevisiae and Caenorhabditis elegans with those of closely related species to elucidate the recent evolutionary history of their respective protein interaction networks. Interaction and expression data are studied in the light of a detailed phylogenetic analysis. The underlying network structure is incorporated explicitly into the statistical analysis. The increased phylogenetic resolution, paired with high-quality interaction data, allows us to resolve the way in which protein interaction network structure and abundance of proteins affect the evolutionary rate. We find that expression levels are better predictors of the evolutionary rate than a protein's connectivity. Detailed analysis of the two organisms also shows that the evolutionary rates of interacting proteins are not sufficiently similar to be mutually predictive. It appears that meaningful inferences about the evolution of protein interaction networks require comparative analysis of reasonably closely related species. The signature of protein evolution is shaped by a protein's abundance in the organism and its function and the biological process it is involved in. Its position in the interaction networks and its connectivity may modulate this but they appear to have only minor influence on a protein's evolutionary rate.

Crosstalk between transcription factors and microRNAs in human protein interaction network.

Abstract: Background Gene regulatory networks control the global gene expression and the dynamics of protein output in living cells. In multicellular organisms, transcription factors and microRNAs are the major families of gene regulators. Recent studies have suggested that these two kinds of regulators share similar regulatory logics and participate in cooperative activities in the gene regulatory network; however, their combinational regulatory effects and preferences on the protein interaction network remain unclear.

How Förster resonance energy transfer imaging improves the understanding of protein interaction networks in cancer biology.

Abstract: Herein we discuss how FRET imaging can contribute at various stages to delineate the function of the proteome. Therefore, we briefly describe FRET imaging techniques, the selection of suitable FRET pairs and potential caveats. Furthermore, we discuss state-of-the-art FRET-based screening approaches (underpinned by protein interaction network analysis using computational biology) and preclinical intravital FRET-imaging techniques that can be used for functional validation of candidate hits (nodes and edges) from the network screen, as well as measurement of the efficacy of perturbing these nodes/edges by short hairpin RNA (shRNA) and/or small molecule-based approaches.