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UnitedMet利用rna -代谢物共变来估算临床样品中的代谢物水平

原文发布日期：2025-04-18

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摘要翻译：

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UnitedMet利用rna -代谢物共变来估算临床样品中的代谢物水平

UnitedMet harnesses RNA–metabolite covariation to impute metabolite levels in clinical samples

原文发布日期：2025-04-18

英文摘要：

Comprehensively studying metabolism requires metabolite measurements. Such measurements, however, are often unavailable in large cohorts of tissue samples. To address this basic barrier, we propose a Bayesian framework (‘UnitedMet’) that leverages RNA–metabolite covariation to impute otherwise unmeasured metabolite levels from widely available transcriptomic data. UnitedMet is equally capable of imputing whole pool sizes and outcomes of isotope tracing experiments. We apply UnitedMet to investigate the metabolic impact of driver mutations in kidney cancer, identifying an association between BAP1 and a highly oxidative tumor phenotype. We similarly apply UnitedMet to determine that advanced kidney cancers upregulate oxidative phosphorylation relative to early-stage disease, that oxidative metabolism in kidney cancer is associated with inferior outcomes to anti-angiogenic therapy and that kidney cancer metastases demonstrate elevated oxidative phosphorylation. UnitedMet provides a scalable tool for assessing metabolic phenotypes when direct measurements are infeasible, facilitating unexplored avenues for metabolite-focused hypothesis generation.

摘要翻译：

全面分析代谢需要进行代谢物测定。然而，在大量组织样本中，这样的测定往往难以获取。为了克服这一基础障碍，我们提出了一种基于RNA-代谢物相关性的贝叶斯框架（称为‘UnitedMet’），该框架可以从广泛可获得的转录组数据中推断出否则无法测得的代谢物水平。 UnitedMet同样能够推断同位素追踪实验的整个组分大小及其结果。我们应用 UnitedMet 研究了肾癌中驱动突变的代谢影响，发现乙酰胆碱受体1（BAP1）与高度氧化性的肿瘤特征之间存在关联。类似地，我们将 UnitedMet 应用于确定晚期肾癌相对于早期病症而言更倾向于增强有氧磷酸化能力，并发现在肾癌中与抗血管生成治疗相关性较差的氧化代谢与较差预后有关。此外，我们还发现肾癌转移样本表现出更高的有氧磷酸化水平。UnitedMet 提供了一种在无法直接测量代谢物时评估代谢型的可扩展工具，有助于开创新的基于代谢物假设的研究路径。