Deberneh Henock M, Bagherinia Ali, Sadygov Rovshan G
Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University of Blvd, Galveston, TX 77555, USA.
Int J Mol Sci. 2025 Jul 3;26(13):6398. doi: 10.3390/ijms26136398.
Metabolic labeling with deuterated water is used in combination with liquid-chromatography coupled with mass spectrometry to study the turnover rates of individual proteins in vivo. This technique and bioinformatics tools for data analysis quantify the turnover rates of thousands of proteins. Turnover rates change during organismal growth and respond to alterations in the environment and diet. The accurate and statistically significant determination of the turnover rate changes of a protein depend on the variations in the turnover rates of the peptides of the protein. One of the systematic factors contributing to this variability is the dependence of the turnover rates on the number of exchangeable hydrogens of the peptides. This variability (by reducing the statistical power) reduces biological interpretability. Here, we propose a computational approach to eliminate the dependence of the turnover rates on the number of exchangeable hydrogens. This approach enhances the accuracy of turnover rate estimation and may help to support more accurate assessments of biological dynamics and disease mechanisms.
用重水进行代谢标记与液相色谱-质谱联用，用于研究体内单个蛋白质的周转率。这项技术和用于数据分析的生物信息学工具可量化数千种蛋白质的周转率。周转率在生物体生长过程中会发生变化，并对环境和饮食的改变做出反应。蛋白质周转率变化的准确且具有统计学意义的测定取决于该蛋白质肽段周转率的变化。导致这种变异性的一个系统因素是周转率对肽段可交换氢数量的依赖性。这种变异性（通过降低统计效力）降低了生物学可解释性。在此，我们提出一种计算方法来消除周转率对可交换氢数量的依赖性。这种方法提高了周转率估计的准确性，并可能有助于支持对生物动力学和疾病机制进行更准确的评估。
