Patil Sonali, Pincas Hanna, Seto Jeremy, Nudelman German, Nudelman Irina, Sealfon Stuart C
Center for Translational Systems Biology and Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
BMC Syst Biol. 2010 Oct 7;4:137. doi: 10.1186/1752-0509-4-137.
Dendritic cells are antigen-presenting cells that play an essential role in linking the innate and adaptive immune systems. Much research has focused on the signaling pathways triggered upon infection of dendritic cells by various pathogens. The high level of activity in the field makes it desirable to have a pathway-based resource to access the information in the literature. Current pathway diagrams lack either comprehensiveness, or an open-access editorial interface. Hence, there is a need for a dependable, expertly curated knowledgebase that integrates this information into a map of signaling networks.
We have built a detailed diagram of the dendritic cell signaling network, with the goal of providing researchers with a valuable resource and a facile method for community input. Network construction has relied on comprehensive review of the literature and regular updates. The diagram includes detailed depictions of pathways activated downstream of different pathogen recognition receptors such as Toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors and nucleotide-binding oligomerization domain-like receptors. Initially assembled using CellDesigner software, it provides an annotated graphical representation of interactions stored in Systems Biology Mark-up Language. The network, which comprises 249 nodes and 213 edges, has been web-published through the Biological Pathway Publisher software suite. Nodes are annotated with PubMed references and gene-related information, and linked to a public wiki, providing a discussion forum for updates and corrections. To gain more insight into regulatory patterns of dendritic cell signaling, we analyzed the network using graph-theory methods: bifan, feedforward and multi-input convergence motifs were enriched. This emphasis on activating control mechanisms is consonant with a network that subserves persistent and coordinated responses to pathogen detection.
This map represents a navigable aid for presenting a consensus view of the current knowledge on dendritic cell signaling that can be continuously improved through contributions of research community experts. Because the map is available in a machine readable format, it can be edited and may assist researchers in data analysis. Furthermore, the availability of a comprehensive knowledgebase might help further research in this area such as vaccine development. The dendritic cell signaling knowledgebase is accessible at http://tsb.mssm.edu/pathwayPublisher/DC_pathway/DC_pathway_index.html.
树突状细胞是抗原呈递细胞，在连接固有免疫系统和适应性免疫系统方面发挥着重要作用。许多研究都集中在各种病原体感染树突状细胞后触发的信号通路。该领域的高度活跃使得需要一个基于通路的资源来获取文献中的信息。当前的通路图要么缺乏全面性，要么缺乏开放获取的编辑界面。因此，需要一个可靠的、经过专家精心策划的知识库，将这些信息整合到信号网络图谱中。
我们构建了树突状细胞信号网络的详细图谱，目的是为研究人员提供一个有价值的资源以及一种便于社区输入的方法。网络构建依赖于对文献的全面综述和定期更新。该图谱包括对不同病原体识别受体（如Toll样受体、视黄酸诱导基因-I样受体、C型凝集素受体和核苷酸结合寡聚化结构域样受体）下游激活的通路的详细描绘。最初使用CellDesigner软件组装，它以系统生物学标记语言存储的相互作用提供了带注释的图形表示。该网络由249个节点和213条边组成，已通过生物通路发布者软件套件在网上发布。节点用PubMed参考文献和基因相关信息进行注释，并链接到一个公共维基，提供一个用于更新和校正的讨论论坛。为了更深入了解树突状细胞信号的调控模式，我们使用图论方法分析了该网络：双扇形、前馈和多输入汇聚基序得到了富集。这种对激活控制机制的强调与一个有助于对病原体检测做出持续和协调反应的网络是一致的。
该图谱是一种可导航的辅助工具，用于呈现关于树突状细胞信号的当前知识的共识观点，可通过研究社区专家的贡献不断改进。由于该图谱以机器可读格式提供，它可以被编辑，并可能协助研究人员进行数据分析。此外，一个全面知识库的可用性可能有助于该领域的进一步研究，如疫苗开发。树突状细胞信号知识库可在http://tsb.mssm.edu/pathwayPublisher/DC_pathway/DC_pathway_index.html上访问。
