Dataset Information

Monitoring the prolonged Tnf stimulation in space and time with topological-functional networks.

ABSTRACT: Genes in linear proximity often share regulatory inputs, expression and evolutionary patterns, even in complex eukaryote genomes with extensive intergenic sequences. Gene regulation, on the other hand, is effected through the co-ordinated activation (or suppression) of genes participating in common biological pathways, which are often transcribed from distant loci. Existing approaches for the study of gene expression focus on the functional aspect, taking positional constraints into account only marginally. In this work we propose a novel concept for the study of gene expression, through the combination of topological and functional information into bipartite networks. Starting from genome-wide expression profiles, we define extended chromosomal regions with consistent patterns of differential gene expression and then associate these domains with enriched functional pathways. By analyzing the resulting networks in terms of size, connectivity and modularity we can draw conclusions on the way genome organization may underlie the gene regulation program. Implementation of this approach in a detailed RNASeq profiling of sustained Tnf stimulation of mouse synovial fibroblasts, allowed us to identify unexpected regulatory changes taking place in the cells after 24?h of stimulation. Bipartite network analysis suggests that the cytokine response set by Tnf, progresses through two distinct transitions. An early generalization of the inflammatory response, that is followed by a late shutdown of immune-related functions and the redistribution of expression to developmental and cell adhesion pathways and distinct chromosomal regions. We show that the incorporation of topological information may provide additional insights in the complex propagation of Tnf activation.

SUBMITTER: Mavropoulos Papoudas S

PROVIDER: S-EPMC6994266 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Monitoring the prolonged Tnf stimulation in space and time with topological-functional networks.

Mavropoulos Papoudas Stylianos S Papanikolaou Nikolaos N Nikolaou Christoforos C

Computational and structural biotechnology journal 20200118

Genes in linear proximity often share regulatory inputs, expression and evolutionary patterns, even in complex eukaryote genomes with extensive intergenic sequences. Gene regulation, on the other hand, is effected through the co-ordinated activation (or suppression) of genes participating in common biological pathways, which are often transcribed from distant loci. Existing approaches for the study of gene expression focus on the functional aspect, taking positional constraints into account only ...[more]

PMID: 32021663

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Project description:BackgroundCommunity detection algorithms are fundamental tools to uncover important features in networks. There are several studies focused on social networks but only a few deal with biological networks. Directly or indirectly, most of the methods maximize modularity, a measure of the density of links within communities as compared to links between communities.ResultsHere we analyze six different community detection algorithms, namely, Combo, Conclude, Fast Greedy, Leading Eigen, Louvain and Spinglass, on two important biological networks to find their communities and evaluate the results in terms of topological and functional features through Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology term enrichment analysis. At a high level, the main assessment criteria are 1) appropriate community size (neither too small nor too large), 2) representation within the community of only one or two broad biological functions, 3) most genes from the network belonging to a pathway should also belong to only one or two communities, and 4) performance speed. The first network in this study is a network of Protein-Protein Interactions (PPI) in Saccharomyces cerevisiae (Yeast) with 6532 nodes and 229,696 edges and the second is a network of PPI in Homo sapiens (Human) with 20,644 nodes and 241,008 edges. All six methods perform well, i.e., find reasonably sized and biologically interpretable communities, for the Yeast PPI network but the Conclude method does not find reasonably sized communities for the Human PPI network. Louvain method maximizes modularity by using an agglomerative approach, and is the fastest method for community detection. For the Yeast PPI network, the results of Spinglass method are most similar to the results of Louvain method with regard to the size of communities and core pathways they identify, whereas for the Human PPI network, Combo and Spinglass methods yield the most similar results, with Louvain being the next closest.ConclusionsFor Yeast and Human PPI networks, Louvain method is likely the best method to find communities in terms of detecting known core pathways in a reasonable time.

Dataset Information

Monitoring the prolonged Tnf stimulation in space and time with topological-functional networks.

Publications

Monitoring the prolonged Tnf stimulation in space and time with topological-functional networks.

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