Advances in technologies and biological applications of ¹⁸O labeling strategies in LC-MS based proteomics: An updated review

A number of stable isotope labeling techniques have been developed and have become the most prospective approaches in the realm of shotgun differential proteomics, where mass spectrometry is often coupled with liquid chromatography for better sensitivity, efficiency and specificity. Among these stable isotope labeling techniques, ¹⁸O labeling has received growing interest in the research community due to its simplicity and applicability. This review focuses on recent advances on methodologies regarding ¹⁸O labeling, such as the use of ultrasonic energy for rapid labeling, non-enzyme mediated ¹⁸O labeling, isotope precursors other than ¹⁸O water, and new tools for data processing, etc. Recent biological applications of ¹⁸O labeling on quantitative proteomics, especially profiling and quantifying several types of posttranslational modifications, are also discussed.