Dynamic changes in protein functional linkage networks revealed by integration with gene expression data

• Published in: PLoS computational biology Vol. 4; no. 11; p. e1000237
• Main Authors: Hegde, Shubhada R, Manimaran, Palanisamy, Mande, Shekhar C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-11-2008; Public Library of Science (PLoS)
• Subjects: Algorithms; Comparative analysis; Computational biology; Computational Biology - methods; Computational Biology/Genomics; Computational Biology/Systems Biology; Computer Simulation; Data processing; Databases, Genetic; E coli; Environmental conditions; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli - radiation effects; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Gene Expression; Gene Regulatory Networks; Genetics; Genomes; Oligonucleotide Array Sequence Analysis - methods; Organisms; Principal components analysis; Protein Binding; Protein Interaction Mapping - methods; Protein-protein interactions; Proteins; Scholarships & fellowships; Ultraviolet Rays; India; Gene Expression; Algorithms; Escherichia coli Proteins; Ultraviolet Rays; Oligonucleotide Array Sequence Analysis; Computer Simulation; Escherichia coli; Computational Biology; Databases, Genetic; Protein Binding; Gene Regulatory Networks; Protein Interaction Mapping
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1000237

Response of cells to changing environmental conditions is governed by the dynamics of intricate biomolecular interactions. It may be reasonable to assume, proteins being the dominant macromolecules that carry out routine cellular functions, that understanding the dynamics of protein:protein interactions might yield useful insights into the cellular responses. The large-scale protein interaction data sets are, however, unable to capture the changes in the profile of protein:protein interactions. In order to understand how these interactions change dynamically, we have constructed conditional protein linkages for Escherichia coli by integrating functional linkages and gene expression information. As a case study, we have chosen to analyze UV exposure in wild-type and SOS deficient E. coli at 20 minutes post irradiation. The conditional networks exhibit similar topological properties. Although the global topological properties of the networks are similar, many subtle local changes are observed, which are suggestive of the cellular response to the perturbations. Some such changes correspond to differences in the path lengths among the nodes of carbohydrate metabolism correlating with its loss in efficiency in the UV treated cells. Similarly, expression of hubs under unique conditions reflects the importance of these genes. Various centrality measures applied to the networks indicate increased importance for replication, repair, and other stress proteins for the cells under UV treatment, as anticipated. We thus propose a novel approach for studying an organism at the systems level by integrating genome-wide functional linkages and the gene expression data.