NetPath: A public resource of curated signal transduction pathways

Institute of Bioinformatics, International Tech Park, Bangalore 560066, India.
Genome biology (Impact Factor: 10.81). 01/2010; 11(1):R3. DOI: 10.1186/gb-2010-11-1-r3
Source: PubMed


We have developed NetPath as a resource of curated human signaling pathways. As an initial step, NetPath provides detailed maps of a number of immune signaling pathways, which include approximately 1,600 reactions annotated from the literature and more than 2,800 instances of transcriptionally regulated genes - all linked to over 5,500 published articles. We anticipate NetPath to become a consolidated resource for human signaling pathways that should enable systems biology approaches.

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Available from: Osamu Ohara
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    • "We first investigated in which signalling pathways the 15 RASopathy proteins participate by using the NetPath/NetSlim database (a manually curated resource that lists 33 signalling pathways; Kandasamy et al, 2010). As RASopathy genes are involved in multiple phenotypical disorders with many diverse and overlapping and clinical symptoms (Supplementary Fig S1), we expected that the 15 proteins are participating in most if not all signalling pathways. "
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    ABSTRACT: The Ras/MAPK syndromes (‘RASopathies’) are a class of developmental disorders caused by germline mutations in 15 genes encoding proteins of the Ras/mitogen-activated protein kinase (MAPK) pathway frequently involved in cancer. Little is known about the molecular mechanisms underlying the differences in mutations of the same protein causing either cancer or RASopathies. Here, we shed light on 956 RASopathy and cancer missense mutations by combining protein network data with mutational analyses based on 3D structures. Using the protein design algorithm FoldX, we predict that most of the missense mutations with destabilising energies are in structural regions that control the activation of proteins, and only a few are predicted to compromise protein folding. We find a trend that energy changes are higher for cancer compared to RASopathy mutations. Through network modelling, we show that partly compensatory mutations in RASopathies result in only minor downstream pathway deregulation. In summary, we suggest that quantitative rather than qualitative network differences determine the phenotypic outcome of RASopathy compared to cancer mutations.
    Full-text · Article · May 2014 · Molecular Systems Biology
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    • "To streamline and organize data collection from literature, we followed the previously described criteria for the inclusion/exclusion of pathway specific reactions [49] [50]. The data accumulated was submitted to the NetPath signaling pathway resource developed by our group [51]. We then generated a signaling map for this pathway using PathVisio pathway visualization software. "
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    ABSTRACT: Fibroblast growth factor-1 (FGF-1) is a well characterized growth factor among the 22 members of the FGF superfamily in humans. It binds to all the four known FGF receptors and regulates a plethora of functions including cell growth, proliferation, migration, differentiation, and survival in different cell types. FGF-1 is involved in the regulation of diverse physiological processes such as development, angiogenesis, wound healing, adipogenesis, and neurogenesis. Deregulation of FGF-1 signaling is not only implicated in tumorigenesis but also is associated with tumor invasion and metastasis. Given the biomedical significance of FGFs and the fact that individual FGFs have different roles in diverse physiological processes, the analysis of signaling pathways induced by the binding of specific FGFs to their cognate receptors demands more focused efforts. Currently, there are no resources in the public domain that facilitate the analysis of signaling pathways induced by individual FGFs in the FGF/FGFR signaling system. Towards this, we have developed a resource of signaling reactions triggered by FGF-1/FGFR system in various cell types/tissues. The pathway data and the reaction map are made available for download in different community standard data exchange formats through NetPath and NetSlim signaling pathway resources.
    Full-text · Article · Apr 2014
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    • "Finally, we note that the interactions included in this library are not all unique to FcεRI signaling and are shared by pathways operative in TCR and BCR signaling. Thus, to facilitate identification of rules applicable to multiple pathways/cell types, in Table S1 in Supplementary Material, we list protein–protein interactions included in the FcεRI library and whether each interaction is part of TCR and BCR signaling according to the NetPath database (41). "
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    ABSTRACT: Antigen receptors play a central role in adaptive immune responses. Although the molecular networks associated with these receptors have been extensively studied, we currently lack a systems-level understanding of how combinations of non-covalent interactions and post-translational modifications are regulated during signaling to impact cellular decision-making. To fill this knowledge gap, it will be necessary to formalize and piece together information about individual molecular mechanisms to form large-scale computational models of signaling networks. To this end, we have developed an interaction library for signaling by the high-affinity IgE receptor, FcεRI. The library consists of executable rules for protein-protein and protein-lipid interactions. This library extends earlier models for FcεRI signaling and introduces new interactions that have not previously been considered in a model. Thus, this interaction library is a toolkit with which existing models can be expanded and from which new models can be built. As an example, we present models of branching pathways from the adaptor protein Lat, which influence production of the phospholipid PIP3 at the plasma membrane and the soluble second messenger IP3. We find that inclusion of a positive feedback loop gives rise to a bistable switch, which may ensure robust responses to stimulation above a threshold level. In addition, the library is visualized to facilitate understanding of network circuitry and identification of network motifs.
    Full-text · Article · Apr 2014 · Frontiers in Immunology
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