Computer Technologies Laboratory, ITMO University, Saint Petersburg, Russia 197101, Russia.
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow 119334, Russia.
Nucleic Acids Res. 2022 Jul 5;50(W1):W690-W696. doi: 10.1093/nar/gkac427.
Multiple high-throughput omics techniques provide different angles on systematically quantifying and studying metabolic regulation of cellular processes. However, an unbiased analysis of such data and, in particular, integration of multiple types of data remains a challenge. Previously, for this purpose we developed GAM web-service for integrative metabolic network analysis. Here we describe an updated pipeline GATOM and the corresponding web-service Shiny GATOM, which takes as input transcriptional and/or metabolomic data and finds a metabolic subnetwork most regulated between the two conditions of interest. GATOM features a new metabolic network topology based on atom transition, which significantly improves interpretability of the analysis results. To address computational challenges arising with the new network topology, we introduce a new variant of the maximum weight connected subgraph problem and provide a corresponding exact solver. To make the used networks up-to-date we upgraded the KEGG-based network construction pipeline and developed one based on the Rhea database, which allows analysis of lipidomics data. Finally, we simplified local installation, providing R package mwcsr for solving relevant graph optimization problems and R package gatom, which implements the GATOM pipeline. The web-service is available at https://ctlab.itmo.ru/shiny/gatom and https://artyomovlab.wustl.edu/shiny/gatom.
多种高通量组学技术为系统地量化和研究细胞过程的代谢调控提供了不同的角度。然而，对这些数据进行无偏分析，特别是整合多种类型的数据仍然是一个挑战。此前，我们为实现这一目的开发了用于综合代谢网络分析的 GAM 网络服务。在这里，我们描述了一个更新的管道 GATOM 及其相应的 Shiny GATOM 网络服务，该服务可接受转录组学和/或代谢组学数据作为输入，并找到在两个感兴趣条件之间调节作用最大的代谢子网络。GATOM 的特点是基于原子跃迁的新代谢网络拓扑结构，这显著提高了分析结果的可解释性。为了解决新网络拓扑结构所带来的计算挑战，我们引入了最大权重连通子图问题的新变体，并提供了相应的精确求解器。为了使所使用的网络保持最新，我们升级了基于 KEGG 的网络构建管道，并开发了一个基于 Rhea 数据库的管道，该管道允许分析脂质组学数据。最后，我们简化了本地安装，提供了用于解决相关图优化问题的 R 包 mwcsr 和实现 GATOM 管道的 R 包 gatom。该网络服务可在 https://ctlab.itmo.ru/shiny/gatom 和 https://artyomovlab.wustl.edu/shiny/gatom 上访问。
