Mitchell Joshua M, Chi Yuanye, Zheng Shujian, Thapa Maheshwor, Wang Eric, Li Shuzhao
The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, Connecticut 06032, United States.
University of Connecticut School of Medicine, Farmington, Connecticut 06032, United States.
J Am Soc Mass Spectrom. 2024 Dec 4;35(12):2824-2835. doi: 10.1021/jasms.4c00175. Epub 2024 Sep 30.
Stable isotope tracing is a crucial technique for understanding the metabolic wiring of biological systems, determining metabolic flux through pathways of interest, and detecting novel metabolites and pathways. Despite the potential insights provided by this technique, its application remains limited to a small number of targeted molecules and pathways. Because previous software tools usually require chemical formulas to find relevant features, and the data are highly complex, especially in untargeted metabolomics and when the downstream reactions and metabolites are poorly characterized. We report here Khipu version 2 and its new user-friendly web application. New functions are added to enhance analyzing stable isotope tracing data including metrics that evaluate peak enrichment in labeled samples, scoring methods to facilitate robust detection of intensity patterns and integrated natural abundance correction. We demonstrate that this approach can be applied to untargeted metabolomics to systematically extract isotope-labeled compounds and annotate the unidentified metabolites.
稳定同位素示踪是一种关键技术，用于理解生物系统的代谢网络、确定通过感兴趣途径的代谢通量，以及检测新的代谢物和途径。尽管该技术能提供潜在的深刻见解，但其应用仍局限于少数目标分子和途径。因为以前的软件工具通常需要化学式来查找相关特征，而且数据高度复杂，特别是在非靶向代谢组学中以及当下游反应和代谢物特征不明确时。我们在此报告Khipu版本2及其新的用户友好型网络应用程序。添加了新功能以增强对稳定同位素示踪数据的分析，包括评估标记样品中峰富集的指标、便于稳健检测强度模式的评分方法以及综合自然丰度校正。我们证明这种方法可应用于非靶向代谢组学，以系统地提取同位素标记的化合物并注释未鉴定的代谢物。
