Dataset Information

Detecting Rewiring Events in Protein-Protein Interaction Networks Based on Transcriptomic Data.

ABSTRACT: Proteins rarely carry out their cellular functions in isolation. Instead, eukaryotic proteins engage in about six interactions with other proteins on average. The aggregated protein interactome of an organism forms a "hairy ball"-type protein-protein interaction (PPI) network. Yet, in a typical human cell, only about half of all proteins are expressed at a particular time. Hence, it has become common practice to prune the full PPI network to the subset of expressed proteins. If RNAseq data is available, one can further resolve the specific protein isoforms present in a cell or tissue. Here, we review various approaches, software tools and webservices that enable users to construct context-specific or tissue-specific PPI networks and how these are rewired between two cellular conditions. We illustrate their different functionalities on the example of the interactions involving the human TNR6 protein. In an outlook, we describe how PPI networks may be integrated with epigenetic data or with data on the activity of splicing factors.

SUBMITTER: Hollander M

PROVIDER: S-EPMC9581068 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Detecting Rewiring Events in Protein-Protein Interaction Networks Based on Transcriptomic Data.

Hollander Markus M Do Trang T Will Thorsten T Helms Volkhard V

Frontiers in bioinformatics 20210908

Proteins rarely carry out their cellular functions in isolation. Instead, eukaryotic proteins engage in about six interactions with other proteins on average. The aggregated protein interactome of an organism forms a "hairy ball"-type protein-protein interaction (PPI) network. Yet, in a typical human cell, only about half of all proteins are expressed at a particular time. Hence, it has become common practice to prune the full PPI network to the subset of expressed proteins. If RNAseq data is av ...[more]

PMID: 36303788

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Project description:BackgroundModeling biological networks serves as both a major goal and an effective tool of systems biology in studying mechanisms that orchestrate the activities of gene products in cells. Biological networks are context-specific and dynamic in nature. To systematically characterize the selectively activated regulatory components and mechanisms, modeling tools must be able to effectively distinguish significant rewiring from random background fluctuations. While differential networks cannot be constructed by existing knowledge alone, novel incorporation of prior knowledge into data-driven approaches can improve the robustness and biological relevance of network inference. However, the major unresolved roadblocks include: big solution space but a small sample size; highly complex networks; imperfect prior knowledge; missing significance assessment; and heuristic structural parameter learning.ResultsTo address these challenges, we formulated the inference of differential dependency networks that incorporate both conditional data and prior knowledge as a convex optimization problem, and developed an efficient learning algorithm to jointly infer the conserved biological network and the significant rewiring across different conditions. We used a novel sampling scheme to estimate the expected error rate due to "random" knowledge. Based on that scheme, we developed a strategy that fully exploits the benefit of this data-knowledge integrated approach. We demonstrated and validated the principle and performance of our method using synthetic datasets. We then applied our method to yeast cell line and breast cancer microarray data and obtained biologically plausible results. The open-source R software package and the experimental data are freely available at http://www.cbil.ece.vt.edu/software.htm.ConclusionsExperiments on both synthetic and real data demonstrate the effectiveness of the knowledge-fused differential dependency network in revealing the statistically significant rewiring in biological networks. The method efficiently leverages data-driven evidence and existing biological knowledge while remaining robust to the false positive edges in the prior knowledge. The identified network rewiring events are supported by previous studies in the literature and also provide new mechanistic insight into the biological systems. We expect the knowledge-fused differential dependency network analysis, together with the open-source R package, to be an important and useful bioinformatics tool in biological network analyses.

Dataset Information

Detecting Rewiring Events in Protein-Protein Interaction Networks Based on Transcriptomic Data.

Publications

Detecting Rewiring Events in Protein-Protein Interaction Networks Based on Transcriptomic Data.

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