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This lecture covers proteomics profiling methods, focusing on activity-based protein profiling (ABPP) and its applications in live cells and lysate. It discusses the use of chemical ligandability and actionability to map the local proteome, REX technologies, APEX, and biotin-streptavidin pulldown. The instructor explains the workflow of bottom-up mass spectrometry (MS) approaches, including peptide digestion, tandem MS, and different fragmentation methods. Additionally, it explores quantitative target identification using SILAC and TMT labeling approaches, highlighting the advantages and differences between them. The lecture concludes with a discussion on the limitations of MS-based approaches and the importance of advanced concepts like ABPP for target/ligand identification.