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Abstract:
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Intracellular enzymes are common targets for therapeutic intervention. Some classes of enzymes, however, are active only in specific conditions or cell types. Activity-based protein profiling (ABPP) is an assay strategy in functional proteomics to isolate active enzymes for study, increasing sensitivity for identification of candidate targets against a background of more numerous but relatively inactive enzymatic counterparts.
We provide an overview of mass spectrometry, which underlies activity-based protein profiling, then discuss two complementary statistical modeling approaches to ABPP screening. Implementation and visualization of results from these models are explored via extensions of established open-source tools. Finally, scientific questions are addressed using the models presented to quantify salient experimental effects, along with strategies to rank results for follow-up. The central roles of experimental design, graphical investigation, and open-source software are emphasized.
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