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Keywords {🔍}

pubmed, signalink, article, signaling, pathway, pathways, proteins, interactions, google, scholar, cas, network, interaction, protein, data, central, database, mirnas, axin, regulatory, networks, figure, components, notch, integrated, tgfβ, tfs, ppis, information, download, transcription, resources, resource, scores, crosstalks, transcriptional, drug, layers, users, original, res, table, scaffold, cell, posttranscriptional, file, shown, nucleic, acids, regulators,

Topics {✒️}

open-access community-driven resource open access article cellular signalling networks drug discovery analyses multi-layered regulatory networks fine-tuned autoregulatory loops multi-level cross-talk network cellular signalling network cis-regulatory sequence annotation post-transcriptional regulatory networks multi-layered signaling network mirna-mediated gene silencing open-access database portales-casamar common signaling-related functions signaling-related network medicine combines large-scale datasets article download pdf cell-signalling dynamics tissue-specific localization information multi-layered database structure identify signalling pathway multi-level cross-talk design multi-target drugs gene regulatory networks transcription-mediated cross-talks post-transcriptional regulatory components semantic similarity-based method single biochemical species full size image target-search options signaling-related endocytosis reviews drug-therapy networks analyze pathway cross-talks post-transcriptional cross-talks post-transcriptional regulatory interactions scoring protein-protein interactions multilevel regulatory networks tf-mirna regulatory interactions human protein-protein interactions nrf2-related interactome tgf-β pathway components analyzing cross-species data allo-network drugs context-dependent transcriptional regulations gene regulatory network search field helps transcription-mediated pathway connections insulin growth factor cross-regulation involving notch

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         headline:SignaLink 2 – a signaling pathway resource with multi-layered regulatory networks
         description:Signaling networks in eukaryotes are made up of upstream and downstream subnetworks. The upstream subnetwork contains the intertwined network of signaling pathways, while the downstream regulatory part contains transcription factors and their binding sites on the DNA as well as microRNAs and their mRNA targets. Currently, most signaling and regulatory databases contain only a subsection of this network, making comprehensive analyses highly time-consuming and dependent on specific data handling expertise. The need for detailed mapping of signaling systems is also supported by the fact that several drug development failures were caused by undiscovered cross-talk or regulatory effects of drug targets. We previously created a uniformly curated signaling pathway resource, SignaLink, to facilitate the analysis of pathway cross-talks. Here, we present SignaLink 2, which significantly extends the coverage and applications of its predecessor. We developed a novel concept to integrate and utilize different subsections (i.e., layers) of the signaling network. The multi-layered (onion-like) database structure is made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network. Compared to other signaling resources, distinctive features of SignaLink 2 are the following: 1) it involves experimental data not only from humans but from two invertebrate model organisms, C. elegans and D. melanogaster; 2) combines manual curation with large-scale datasets; 3) provides confidence scores for each interaction; 4) operates a customizable download page with multiple file formats (e.g., BioPAX, Cytoscape, SBML). Non-profit users can access SignaLink 2 free of charge at http://SignaLink.org . With SignaLink 2 as a single resource, users can effectively analyze signaling pathways, scaffold proteins, modifier enzymes, transcription factors and miRNAs that are important in the regulation of signaling processes. This integrated resource allows the systems-level examination of how cross-talks and signaling flow are regulated, as well as provide data for cross-species comparisons and drug discovery analyses.
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         Algorithms
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      affiliation:
            name:Statistical and Biological Physics Group of the Hungarian Acad. of Sciences
            address:
               name:Statistical and Biological Physics Group of the Hungarian Acad. of Sciences, Budapest, Hungary
               type:PostalAddress
            type:Organization
            name:Department of Biological Physics, Eötvös Loránd University
            address:
               name:Department of Biological Physics, Eötvös Loránd University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Dénes Türei
      affiliation:
            name:Eötvös Loránd University
            address:
               name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
               type:PostalAddress
            type:Organization
            name:Semmelweis University
            address:
               name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Dezső Módos
      affiliation:
            name:Eötvös Loránd University
            address:
               name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
               type:PostalAddress
            type:Organization
            name:Semmelweis University
            address:
               name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
               type:PostalAddress
            type:Organization
            name:Semmelweis University
            address:
               name:Department of Morphology and Physiology, Semmelweis University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Máté Pálfy
      affiliation:
            name:Eötvös Loránd University
            address:
               name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Zoltán Dúl
      affiliation:
            name:Eötvös Loránd University
            address:
               name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
               type:PostalAddress
            type:Organization
            name:Semmelweis University
            address:
               name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Lilian Zsákai
      affiliation:
            name:Eötvös Loránd University
            address:
               name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
               type:PostalAddress
            type:Organization
            name:Semmelweis University
            address:
               name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Máté Szalay-Bekő
      affiliation:
            name:Semmelweis University
            address:
               name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Katalin Lenti
      affiliation:
            name:Eötvös Loránd University
            address:
               name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
               type:PostalAddress
            type:Organization
            name:Semmelweis University
            address:
               name:Department of Morphology and Physiology, Semmelweis University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Illés J Farkas
      affiliation:
            name:Statistical and Biological Physics Group of the Hungarian Acad. of Sciences
            address:
               name:Statistical and Biological Physics Group of the Hungarian Acad. of Sciences, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Tibor Vellai
      affiliation:
            name:Eötvös Loránd University
            address:
               name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Péter Csermely
      affiliation:
            name:Semmelweis University
            address:
               name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      name:Tamás Korcsmáros
      affiliation:
            name:Eötvös Loránd University
            address:
               name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
               type:PostalAddress
            type:Organization
            name:Semmelweis University
            address:
               name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
      name:Statistical and Biological Physics Group of the Hungarian Acad. of Sciences, Budapest, Hungary
      name:Department of Biological Physics, Eötvös Loránd University, Budapest, Hungary
      name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
      name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
      name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
      name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
      name:Department of Morphology and Physiology, Semmelweis University, Budapest, Hungary
      name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
      name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
      name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
      name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
      name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
      name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
      name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
      name:Department of Morphology and Physiology, Semmelweis University, Budapest, Hungary
      name:Statistical and Biological Physics Group of the Hungarian Acad. of Sciences, Budapest, Hungary
      name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
      name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary
      name:Department of Genetics, Eötvös Loránd University, Budapest, Hungary
      name:Department of Medical Chemistry, Semmelweis University, Budapest, Hungary

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