[hijodelsol]

While interesting, I think that the relevance of MassSpec based approaches will decline over the next years.

Single cell genomics already had to learn the hard lesson that pure gene quantification and big data approaches without spatial resolution or deep understanding of the biology can only get you so far. Billions have been spent on cell atlases that just deal with biology as individual cells without much to show for in terms of changes in clinical practice. Spatial omics is now finally spreading and spatial organization and interactions are being taken into account again, but the common analysis pipeline still just focus on gene level expression at the cellular level. Subcellular and extracellular information is often completely lost and gene levels are highly variant and only somewhat correlate with the phosphoproteome, the actual effect layer of biology.

Mass spec approaches share many of the same limitations, even though they deal with protein. Spatial information is blurry at best or lost at worst and equipment is expensive and requires specialized training.

Imo, the most interesting advances in the next years will come from low cost high resolution spatial proteomics with high target counts that integrate with biological modeling of processes.

[getoffmycase]

I disagree. I think that proteomics is useful without spatial information because it captures a snapshot of cell state, or tissue state rather, of signaling networks via PTMs along with abundance measurements. If you don’t have spatial orientation, you at least have temporal information.

I think increasing the yield of MS2 scans to PSMs specifically by dealing with spectra containing PTMs and chimeric spectra will further enable deeper understanding of cell signaling. Additionally, the targeted analysis of specific sub-proteomes using real time search, using GoDig from the Gygi lab for example, also seems very promising.

Plus, there’s large industry efforts using proteomics as a drug screening tool, an application that doesn’t require spatial resolution of anything. Specifically groups are looking for protein expression knockdown, but it’s not too far a stretch to look for pathway perturbations using real time search and careful controls.