Institute for Biostatistics and Informatics in Medicine and Ageing Research, University of Rostock, Rostock, Germany.
PLoS One. 2010 Dec 10;5(12):e15165. doi: 10.1371/journal.pone.0015165.
Analysis of the mechanisms underlying pluripotency and reprogramming would benefit substantially from easy access to an electronic network of genes, proteins and mechanisms. Moreover, interpreting gene expression data needs to move beyond just the identification of the up-/downregulation of key genes and of overrepresented processes and pathways, towards clarifying the essential effects of the experiment in molecular terms.
METHODOLOGY/PRINCIPAL FINDINGS: We have assembled a network of 574 molecular interactions, stimulations and inhibitions, based on a collection of research data from 177 publications until June 2010, involving 274 mouse genes/proteins, all in a standard electronic format, enabling analyses by readily available software such as Cytoscape and its plugins. The network includes the core circuit of Oct4 (Pou5f1), Sox2 and Nanog, its periphery (such as Stat3, Klf4, Esrrb, and c-Myc), connections to upstream signaling pathways (such as Activin, WNT, FGF, BMP, Insulin, Notch and LIF), and epigenetic regulators as well as some other relevant genes/proteins, such as proteins involved in nuclear import/export. We describe the general properties of the network, as well as a Gene Ontology analysis of the genes included. We use several expression data sets to condense the network to a set of network links that are affected in the course of an experiment, yielding hypotheses about the underlying mechanisms.
CONCLUSIONS/SIGNIFICANCE: We have initiated an electronic data repository that will be useful to understand pluripotency and to facilitate the interpretation of high-throughput data. To keep up with the growth of knowledge on the fundamental processes of pluripotency and reprogramming, we suggest to combine Wiki and social networking software towards a community curation system that is easy to use and flexible, and tailored to provide a benefit for the scientist, and to improve communication and exchange of research results. A PluriNetWork tutorial is available at http://www.ibima.med.uni-rostock.de/IBIMA/PluriNetWork/.
对多能性和重编程的机制进行分析将大大受益于能够方便地访问基因、蛋白质和机制的电子网络。此外，解释基因表达数据需要超越仅仅识别关键基因及其过度表达的过程和途径的上调/下调，朝着澄清实验在分子水平上的基本效果的方向发展。
方法/主要发现：我们根据截至 2010 年 6 月的 177 篇出版物中的一组研究数据，组装了一个由 574 个分子相互作用、刺激和抑制组成的网络，涉及 274 个小鼠基因/蛋白质，全部采用标准电子格式，能够通过 Cytoscape 及其插件等现成软件进行分析。该网络包括 Oct4（Pou5f1）、Sox2 和 Nanog 的核心电路，其外围（如 Stat3、Klf4、Esrrb 和 c-Myc），与上游信号通路（如 Activin、WNT、FGF、BMP、胰岛素、Notch 和 LIF）的连接，以及表观遗传调节剂以及其他一些相关基因/蛋白质，如参与核输入/输出的蛋白质。我们描述了网络的一般性质，以及包含的基因的基因本体分析。我们使用几个表达数据集来将网络浓缩为一组在实验过程中受影响的网络链接，从而产生关于潜在机制的假设。
结论/意义：我们已经启动了一个电子数据存储库，这将有助于理解多能性并促进对高通量数据的解释。为了跟上关于多能性和重编程基本过程的知识的增长，我们建议将维基和社交网络软件结合起来，建立一个易于使用且灵活的社区管理系统，旨在为科学家提供好处，并改善沟通和研究结果的交流。PluriNetWork 教程可在 http://www.ibima.med.uni-rostock.de/IBIMA/PluriNetWork/ 获得。
