The proteomic future: where mass spectrometry should be taking us

Abstract

A newcomer to the -omics era, proteomics, is a broad instrument-intensive research area that has advanced rapidly since its inception less than 20 years ago. Although the 'wet-bench' aspects of proteomics have undergone a renaissance with the improvement in protein and peptide separation techniques, including various improvements in two-dimensional gel electrophoresis and gel-free or off-gel protein focusing, it has been the seminal advances in MS that have led to the ascension of this field. Recent improvements in sensitivity, mass accuracy and fragmentation have led to achievements previously only dreamed of, including whole-proteome identification, and quantification and extensive mapping of specific PTMs (post-translational modifications). With such capabilities at present, one might conclude that proteomics has already reached its zenith; however, 'capability' indicates that the envisioned goals have not yet been achieved. In the present review we focus on what we perceive as the areas requiring more attention to achieve the improvements in workflow and instrumentation that will bridge the gap between capability and achievement for at least most proteomes and PTMs. Additionally, it is essential that we extend our ability to understand protein structures, interactions and localizations. Towards these ends, we briefly focus on selected methods and research areas where we anticipate the next wave of proteomic advances.

The Potato Tuber Mitochondrial Proteome

“…The large number of PTM sites on some proteins could give rise to a very large number of differentially modified versions of the protein, unless the PTMs are introduced in an ordered rather than a random manner (Thelen and Miernyk, 2012). A relatively unexplored research area is the interaction between different PTMs.…”

Optimizing the Identification of Citrullinated Peptides by Mass Spectrometry: Utilizing the Inability of Trypsin to Cleave after Citrullinated Amino Acids

“…These posttranslational modifications (PTMs) are often crucial to ensure the correct physiological function of the given protein. More than 200 distinct PTMs have been identified [2]. Furthermore, the PTMs can determine the activity state, localization, turnover, and interaction with other proteins and substrates [1,[3][4][5].…”

Proteome signatures—how are they obtained and what do they teach us?

“…Mass spectrometry itself has also undergone technological advancements. The basic types of mass analyzers remain the quadrupole (Q), the time-of-flight (TOF) analyzer, the ion trap, the Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), and the Orbitrap, but they have suffered significant enhancements which have yielded improvements in sensitivity, accuracy, dynamic range, speed of analysis, and resolution (Thelen and Miernyk 2012). Ion traps, for example, can easily be coupled to hybrid devices, such as Fourier transform-based mass spectrometers (FTMS) to increase resolution and sensitivity (Van Oudenhove and Devreese 2013).…”