SignaLink 2 - a signaling pathway resource with multi-layered regulatory networks.
SignaLink 2 - a signaling pathway resource with multi-layered regulatory networks.
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DOI：
10.1186/1752-0509-7-7
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发表时间：
2013-01-18
影响因子：
--
通讯作者：
Korcsmáros T
中科院分区：
文献类型：
--
作者：
Fazekas D;Koltai M;Türei D;Módos D;Pálfy M;Dúl Z;Zsákai L;Szalay-Bekő M;Lenti K;Farkas IJ;Vellai T;Csermely P;Korcsmáros T
真核生物中的信号网络由上游和下游子网络组成。上游子网络包含相互交织的信号通路网络，而下游调节部分包含转录因子及其在DNA上的结合位点以及microRNA及其mRNA靶标。目前，大多数信令和监管数据库仅包含该网络的一个子部分，使得全面分析非常耗时，并依赖于特定的数据处理专业知识。对信号系统的详细映射的需要也得到了以下事实的支持，即几种药物开发失败是由未发现的药物靶点的串扰或调节作用引起的。我们之前创建了一个统一策划的信号通路资源SignaLink，以促进通路交叉对话的分析。在这里，我们介绍SignaLink 2，它大大扩展了其前身的覆盖范围和应用。我们开发了一个新的概念来整合和利用不同的子部分（即，层）的信令网络。多层（洋葱状）数据库结构由信号传导通路、它们的通路调节剂（例如，支架和内吞蛋白）和修饰酶（例如，磷酸酶、泛素连接酶），以及所有这些组分的转录和转录后调节因子。这个用户友好的网站允许交互式探索每种信号蛋白是如何调节的。可定制的下载页面支持对信令网络的任何用户指定部分进行分析。与其他信号源相比，SignaLink 2的显著特征如下：1）它不仅涉及来自人类的实验数据，还涉及来自两种无脊椎模式生物C. elegans和D.黑腹; 2）将人工策展与大规模数据集相结合; 3）为每个交互提供置信度分数; 4）操作具有多种文件格式的可定制下载页面（例如，BioPAX，Cytoscape，SBML）。非营利用户可以在http://SignaLink.org上免费访问SignaLink 2。使用SignaLink 2作为单一资源，用户可以有效地分析信号传导通路、支架蛋白、修饰酶、转录因子和miRNA，这些在信号传导过程的调节中非常重要。这种综合资源允许系统级检查如何调节交叉对话和信号流，并为跨物种比较和药物发现分析提供数据。
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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影响因子：
3
作者：
Jain S;Bader GD
通讯作者：
Bader GD
影响因子：
14.9
作者：
Blanco E;Farré D;Albà MM;Messeguer X;Guigó R
通讯作者：
Guigó R
影响因子：
4.4
作者：
Bovolenta LA;Acencio ML;Lemke N
通讯作者：
Lemke N
影响因子：
14.9
作者：
Gallo SM;Gerrard DT;Miner D;Simich M;Des Soye B;Bergman CM;Halfon MS
通讯作者：
Halfon MS
DOI：
10.1073/pnas.0409433102
发表时间：
2005-02-08
影响因子：
11.1
作者：
Fisher, J;Piterman, N;Harel, D
通讯作者：
Harel, D