Challenges Remain in MS-based Proteomic Analysis of Complex Biological Samples

October 22, 2014
Challenges Remain in MS-based Proteomic Analysis of Complex Biological Samples
One novel technique for capturing clinically important low-abundance proteins is to create core-shell hydrogel nanoparticles containing high affinity reactive chemical baits for protein and peptide harvesting and concentration. [AlexRaths/iStock Photos]

Patricia Fitzpatrick Dimond, Ph.D.

Many scientists point out that it’s become clear there are no simple universal strategies for the comprehensive analysis of complex proteomes. Although the application of omics technologies to biological samples generates hundreds to thousands of biomarker candidates, a small number actually make it through the pipeline to clinical use, largely due to the incredible mismatch between the large numbers of biomarker candidates and the paucity of reliable assays and methods for validation studies.

Currently, the main technology platform for systematically interrogating large numbers of proteins is based on multiple reaction monitoring (MRM) mass spectrometry (MS). However, a substantial challenge in using MRM-MS for targeted peptide analysis in clinical proteomics applications is the prevalence of interfering peptides and small molecules in the sample matrix. This problem, although well studied for small molecule analysis, is both less well recognized and far more severe for peptide analysis because peptide MRM analyses are typically carried out in an ocean of many hundreds of thousands to millions of peptides produced by digestion of the 10,000 or more proteins found in blood and other tissues.

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