Reconstructing signaling pathways using regular language constrained paths
Reconstructing signaling pathways using regular language constrained paths
复制标题
DOI：
10.1093/bioinformatics/btz360
复制
发表时间：
2019-07-15
期刊：
影响因子：
5.8
通讯作者：
Murali，T. M.
中科院分区：
文献类型：
--
作者：
Wagner，Mitchell J.;Pratapa，Aditya;Murali，T. M.
高质量的蛋白质和信号通路中的相互作用的管理是缓慢和艰苦的。因此，许多实验检测到的相互作用没有注释到任何途径。一个自然出现的问题是，它是否可以自动利用现有的途径注释，以确定新的相互作用，包括在一个给定的pathway.ResultsWe presentRegLinker，算法，实现这一目的，通过计算多个短路径从途径受体转录因子在一个背景相互作用网络。RegLinker的核心思想是使用正则语言约束来控制计算路径中存在的非路径相互作用的数量。我们系统地评估了RegLinker和五种替代方法对一组全面的15个信号通路，并证明了RegLinker恢复保留的通路蛋白和相互作用的最佳精度和召回。我们使用RegLinkerto提出新的扩展途径。我们讨论的文献，支持列入这些蛋白质的途径。这些结果显示了自动化分析在减轻传统手工查询困难方面的广泛潜力。可用性和实施https：github.com/Murali-group/RegLinker.Supplementary信息补充数据可在Bioinformatics在线获得。
MotivationHigh-quality curation of the proteins and interactions in signaling pathways is slow and painstaking. As a result, many experimentally detected interactions are not annotated to any pathways. A natural question that arises is whether or not it is possible to automatically leverage existing pathway annotations to identify new interactions for inclusion in a given pathway.ResultsWe presentRegLinker, an algorithm that achieves this purpose by computing multiple short paths from pathway receptors to transcription factors within a background interaction network. The key idea underlyingRegLinkeris the use of regular language constraints to control the number of non-pathway interactions that are present in the computed paths. We systematically evaluateRegLinkerand five alternative approaches against a comprehensive set of 15 signaling pathways and demonstrate thatRegLinkerrecovers withheld pathway proteins and interactions with the best precision and recall. We usedRegLinkerto propose new extensions to the pathways. We discuss the literature that supports the inclusion of these proteins in the pathways. These results show the broad potential of automated analysis to attenuate difficulties of traditional manual inquiry.Availability and implementationhttps://github.com/Murali-group/RegLinker.Supplementary informationSupplementary data are available atBioinformaticsonline.