Department of Computer Engineering and Informatics, Department of Medical Physics, School of Medicine, University of Patras, Patras 26500, Greece.
Centre for Cancer Biomarkers CCBIO and Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway and.
Bioinformatics. 2016 Mar 15;32(6):884-92. doi: 10.1093/bioinformatics/btv673. Epub 2015 Nov 14.
In the era of network medicine and the rapid growth of paired time series mRNA/microRNA expression experiments, there is an urgent need for pathway enrichment analysis methods able to capture the time- and condition-specific 'active parts' of the biological circuitry as well as the microRNA impact. Current methods ignore the multiple dynamical 'themes'-in the form of enriched biologically relevant microRNA-mediated subpathways-that determine the functionality of signaling networks across time.
To address these challenges, we developed time-vaRying enriCHment integrOmics Subpathway aNalysis tOol (CHRONOS) by integrating time series mRNA/microRNA expression data with KEGG pathway maps and microRNA-target interactions. Specifically, microRNA-mediated subpathway topologies are extracted and evaluated based on the temporal transition and the fold change activity of the linked genes/microRNAs. Further, we provide measures that capture the structural and functional features of subpathways in relation to the complete organism pathway atlas. Our application to synthetic and real data shows that CHRONOS outperforms current subpathway-based methods into unraveling the inherent dynamic properties of pathways.
CHRONOS is freely available at http://biosignal.med.upatras.gr/chronos/
Supplementary data are available at Bioinformatics online.
在网络医学和配对时间序列 mRNA/ microRNA 表达实验快速发展的时代，迫切需要能够捕捉生物电路以及 microRNA 影响的时间和条件特定“活跃部分”的通路富集分析方法。当前的方法忽略了多个动态“主题”——以丰富的生物学相关 microRNA 介导的子途径的形式——这些主题决定了信号网络在整个时间内的功能。
为了解决这些挑战，我们通过将时间序列 mRNA/microRNA 表达数据与 KEGG 通路图谱和 microRNA-靶相互作用集成，开发了时间变化的富集综合子途径分析工具（CHRONOS）。具体来说，基于连接基因/microRNAs 的时间过渡和折叠变化活性来提取和评估 microRNA 介导的子途径拓扑结构。此外，我们提供了一些措施，这些措施可以捕获子途径与完整生物体途径图谱相关的结构和功能特征。我们对合成数据和真实数据的应用表明，CHRONOS 在揭示途径的固有动态特性方面优于当前基于子途径的方法。
CHRONOS 可在 http://biosignal.med.upatras.gr/chronos/ 免费获得。
补充数据可在 Bioinformatics 在线获得。
