Liquid chromatography mass spectrometry-based proteomics: Biological and technological aspects

摘要

Mass spectrometry-based proteomics has become the tool of choice foridentifying and quantifying the proteome of an organism. Though recent yearshave seen a tremendous improvement in instrument performance and thecomputational tools used, significant challenges remain, and there are manyopportunities for statisticians to make important contributions. In the mostwidely used "bottom-up" approach to proteomics, complex mixtures of proteinsare first subjected to enzymatic cleavage, the resulting peptide products areseparated based on chemical or physical properties and analyzed using a massspectrometer. The two fundamental challenges in the analysis of bottom-upMS-based proteomics are as follows: (1) Identifying the proteins that arepresent in a sample, and (2) Quantifying the abundance levels of the identifiedproteins. Both of these challenges require knowledge of the biological andtechnological context that gives rise to observed data, as well as theapplication of sound statistical principles for estimation and inference. Wepresent an overview of bottom-up proteomics and outline the key statisticalissues that arise in protein identification and quantification.