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Adding protein context to the human protein-protein interaction network to reveal meaningful interactions

Schaefer, Martin H ; Lopes, Tiago J S ; Mah, Nancy ; Shoemaker, Jason E ; Matsuoka, Yukiko ; Fontaine, Jean-Fred ; Louis-Jeune, Caroline ; Eisfeld, Amie J ; Neumann, Gabriele ; Perez-Iratxeta, Carol ; Kawaoka, Yoshihiro ; Kitano, Hiroaki ; Andrade-Navarro, Miguel A Rzhetsky, Andrey

PLoS computational biology, 2013-01, Vol.9 (1), p.e1002860-e1002860 [Periódico revisado por pares]

United States: Public Library of Science

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  • Título:
    Adding protein context to the human protein-protein interaction network to reveal meaningful interactions
  • Autor: Schaefer, Martin H ; Lopes, Tiago J S ; Mah, Nancy ; Shoemaker, Jason E ; Matsuoka, Yukiko ; Fontaine, Jean-Fred ; Louis-Jeune, Caroline ; Eisfeld, Amie J ; Neumann, Gabriele ; Perez-Iratxeta, Carol ; Kawaoka, Yoshihiro ; Kitano, Hiroaki ; Andrade-Navarro, Miguel A
  • Rzhetsky, Andrey
  • Assuntos: Alzheimer Disease - metabolism ; Alzheimer's disease ; Alzheimers disease ; Biocatalysis ; Biology ; Cellular signal transduction ; Cytokines ; Gene expression ; Humans ; Infections ; Influenza ; Medicine ; Methods ; Phosphorylation ; Protein Binding ; Protein-protein interactions ; Proteins ; Proteins - metabolism ; Proteome ; Signal Transduction ; Studies ; Viral Proteins - metabolism ; Yeast
  • É parte de: PLoS computational biology, 2013-01, Vol.9 (1), p.e1002860-e1002860
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Conceived and designed the experiments: MHS TJSL YK HK MAAN. Analyzed the data: MHS TJSL NM JES YM JFF CLJ AJE GN CPI. Wrote the paper: MHS TJSL NM AJE GN MAAN.
    The authors have declared that no competing interests exist.
  • Descrição: Interactions of proteins regulate signaling, catalysis, gene expression and many other cellular functions. Therefore, characterizing the entire human interactome is a key effort in current proteomics research. This challenge is complicated by the dynamic nature of protein-protein interactions (PPIs), which are conditional on the cellular context: both interacting proteins must be expressed in the same cell and localized in the same organelle to meet. Additionally, interactions underlie a delicate control of signaling pathways, e.g. by post-translational modifications of the protein partners - hence, many diseases are caused by the perturbation of these mechanisms. Despite the high degree of cell-state specificity of PPIs, many interactions are measured under artificial conditions (e.g. yeast cells are transfected with human genes in yeast two-hybrid assays) or even if detected in a physiological context, this information is missing from the common PPI databases. To overcome these problems, we developed a method that assigns context information to PPIs inferred from various attributes of the interacting proteins: gene expression, functional and disease annotations, and inferred pathways. We demonstrate that context consistency correlates with the experimental reliability of PPIs, which allows us to generate high-confidence tissue- and function-specific subnetworks. We illustrate how these context-filtered networks are enriched in bona fide pathways and disease proteins to prove the ability of context-filters to highlight meaningful interactions with respect to various biological questions. We use this approach to study the lung-specific pathways used by the influenza virus, pointing to IRAK1, BHLHE40 and TOLLIP as potential regulators of influenza virus pathogenicity, and to study the signalling pathways that play a role in Alzheimer's disease, identifying a pathway involving the altered phosphorylation of the Tau protein. Finally, we provide the annotated human PPI network via a web frontend that allows the construction of context-specific networks in several ways.
  • Editor: United States: Public Library of Science
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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