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Tandem mass spectrometry that can be coupled with various separation techniques is a rapid, sensitive, selective, high-throughput methodology capable of the identification of proteins or peptides with posttranslational modifications (PTMs) where other strategies mostly fail. Here, we review the state-of-the-art instrumentation and hyphenating possibilities used for PTM screening and quantitation, currently utilised standard and novel fragmentation techniques, as well as the present and potential applications in clinical and systems biology environment. Finally, we offer specific examples regarding the most prevalent PTM identification approaches.

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