The journey towards clinical adoption of MALDI‐MS‐based imaging proteomics: from current challenges to future expectations

Abstract

Among the spatial omics techniques available, mass spectrometry imaging (MSI) represents one of the most promising owing to its capability to map the distribution of hundreds of peptides and proteins, as well as other classes of biomolecules, within a complex sample background in a multiplexed and relatively high‐throughput manner. In particular, matrix‐assisted laser desorption/ionisation (MALDI‐MSI) has come to the fore and established itself as the most widely used technique in clinical research. However, the march of this technique towards clinical utility has been hindered by issues related to method reproducibility, appropriate biocomputational tools, and data storage. Notwithstanding these challenges, significant progress has been achieved in recent years regarding multiple facets of the technology and has rendered it more suitable for a possible clinical role. As such, there is now more robust and extensive evidence to suggest that the technology has the potential to support clinical decision‐making processes under appropriate circumstances. In this review, we will discuss some of the recent developments that have facilitated this progress and outline some of the more promising clinical proteomics applications which have been developed with a clear goal towards implementation in mind.

Feasibility of MALDI-MSI-Based Proteomics Using Bouin-Fixed Pathology Samples: Untapping the Goldmine of Nephropathology Archives

“…Of note, the advent of spatial proteomics techniques, such as matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), has also permitted in situ molecular mapping of pathological tissue to be integrated with routine histomorphological evaluation, further broadening its application in this field. 2 While the most ideal tissue sources for this process are represented by those that are fresh or have been snap-frozen, resulting in a more native molecular representation of the cells present within the tissue along with improved antigenicity, it can be challenging to achieve widespread application using retrospective pathology archives. For this reason, the development of standardized protocols which have enabled the routine MALDI-MSI proteomics analysis of archived formalin-fixed paraffinembedded (FFPE) tissues has been developed, presenting noninferiority with respect to their fresh or snap-frozen counterparts, 3 and has since been applied to a variety of disease contexts, including renal diseases.…”

“…The introduction of mass spectrometry-based proteomics is gradually impacting various fields of medicine, particularly molecular pathology. Of note, the advent of spatial proteomics techniques, such as matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), has also permitted in situ molecular mapping of pathological tissue to be integrated with routine histomorphological evaluation, further broadening its application in this field . While the most ideal tissue sources for this process are represented by those that are fresh or have been snap-frozen, resulting in a more native molecular representation of the cells present within the tissue along with improved antigenicity, it can be challenging to achieve widespread application using retrospective pathology archives.…”