Zhou Zhiwei, Liu Yuanyuan, Wang Mingxun, Dodd Dylan
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Computer Science and Engineering, University of California Riverside, Riverside, CA, USA.
bioRxiv. 2025 Aug 22:2025.08.18.670916. doi: 10.1101/2025.08.18.670916.
The functional annotation of microbial genes lags far behind genome sequencing, leaving critical gaps in our knowledge of metabolic pathways. While integrating genetic manipulation with stable isotope tracing (SIT) metabolomics holds promise for pathway discovery, existing tools lack specialized capabilities for gene perturbation experiments. To address this need, we developed IsoPairFinder, a computational tool that identifies pathway intermediates by analyzing paired unlabeled (C) and isotope-labeled (C) metabolomics data from gene-edited microbes. By prioritizing substrate-specific feature pairs, IsoPairFinder efficiently prioritizes biologically relevant intermediates. Implemented as an open-source R package and integrated into the GNPS2 ecosystem, IsoPairFinder provides an accessible platform for the research community to accelerate novel pathway discovery and validation.
微生物基因的功能注释远远落后于基因组测序，这使得我们在代谢途径知识方面存在关键空白。虽然将基因操作与稳定同位素示踪（SIT）代谢组学相结合有望用于途径发现，但现有工具缺乏针对基因扰动实验的专门功能。为满足这一需求，我们开发了IsoPairFinder，这是一种计算工具，通过分析来自基因编辑微生物的未标记（C）和同位素标记（C）代谢组学配对数据来识别途径中间体。通过对底物特异性特征对进行优先级排序，IsoPairFinder有效地对生物学相关中间体进行优先级排序。IsoPairFinder作为一个开源R包实现，并集成到GNPS2生态系统中，为研究社区提供了一个易于使用的平台，以加速新途径的发现和验证。
