This week’s Mass Spec News

Essential Reading

Spatial Proteomics Breakthrough 

There was a big breakthrough in the world of spatial proteomics this week, as a global team led by Matthias Mann made a significant discovery in the treatment of toxic epidermal necrolysis (TEN) – an often fatal and previously considered untreatable condition that causes widespread detachment of the skin. 

The new approach, dubbed deep visual proteomics (DVP), combines ultra-sensitive mass spectrometry with microscopy and AI-driven analysis to study specific cell types from  tissue sections to an unprecedented degree of detail. Using DVP, the team identified the hyperactivation of the inflammatory JAK/STAT pathway in samples from patients suffering from TEN, establishing JAK inhibitors as a potential treatment option. When put in practice, JAK inhibitors produced consistent and overwhelmingly positive results.

“I was genuinely surprised by just how powerful DVP proved to be – the fact that we could get such detailed molecular insights using archived tissue biopsies was remarkable,” first author Thierry Nordmann told us in a recent interview. “Without this capability, we would have needed years to prospectively collect enough samples of such a rare disease. 

“The ability to use archived tissue samples opens up entirely new possibilities – we can now study rare diseases where prospective sample collection would take years, or tackle fundamental questions about cellular aging at molecular resolution. I believe we are at a turning point in translational medicine, and we now have the right tools at the right time to fundamentally change how we understand health and treat diseases.”

A full breakdown of the team’s method can be found in this thread on X, if you’re keen to learn more. And our full interview with Nordmann will be posted next week, so be sure to keep an eye out for that too. 
 

“A Whole New Ballpark for Mass Spectrometry”

Last week, as part of our ongoing charge detection mass spectrometry (CD-MS) series, we spoke with Evan Williams (University of California, Berkeley):

“The advantage of CD-MS for large particles is similar to the advantage of conventional mass spectrometry for smaller molecules (below a MDa): it provides very accurate mass measurements, quickly, with high sensitivity and specificity. This is valuable for characterizing anything involving large particles, whether it’s viral particles, synthetic lipid nanoparticles, or other examples we’ve been working on. For instance, we can determine how much RNA is in lipid nanoparticles, what the average size of the particles is, and how they are affected by processes like freezing.”

During the interview, Evan also mentioned that a primary obstacle for “native” MS at the moment is the reliance on non-physiological buffers, such as ammonium acetate (AmmAc). In light of this, Evan and his colleagues recently published a study comparing the effects of AmmAc with alternative salts on the stability of bovine serum albumin in native MS by using electrospray emitters with submicron tips to desalt protein ions. 

Worth Your Time...

Researchers from the Leibniz-Institute for Food Systems Biology develop a quick and efficient LC-MS/MS method to analyze concentrations of peptides formed during cheese ripening to predict maturation-dependent “kokumi” taste. Link

Fluoropolymers release (effectively) no PFAS emissions when destroyed under typical European waste incineration conditions, according to UHPLC-MS/MS and GC-MS analyses. Link

A novel data-driven fingerprint approach for NEMS-MS offers the means to measure individual protein masses using nanoscale devices which, according to author Michael Roukes, offers the potential to “understand the complete proteome of organisms, including humans.” Link

Preprint: Chengyi Xie and colleagues develop a technique to expand MALDI-MS imaging spatial resolution 10-fold, whilst being fully compatible with standard platforms. Link

Preprint: A new algorithm known as “Scalable MBR” provides the ability to search thousands of MS raw files in just a few hours, generating results virtually identical to those using DIA-NN software. Link

Community Corner

Gotham’s Unlikely Hero
 

Twitter user @Muir_Lab pointed out another win for #TeamMassSpec last week, as they discovered the use of GC-MS by Morgan Freeman’s character (Lucius Fox) upon a rewatch of Christopher Nolan’s superhero blockbuster “Batman Begins.”

Do you know which system it is that he’s using? Let us know!