How to Scale Proteomics | Hacker News Reader

How to Scale Proteomics

asimov.press

32 pointssurprisetalk10 comments

I'll admit, my perspective is now 16, almost 17 years out-of-date, but my read of this article is that nothing much has advanced beyond what I was doing in the field back then.

My job? Data plumber and analyst, same as now. I scripted the nuts-and-bolts of matching the mass/time/time data off the instrument being developed by much more qualified PhD candidates and their advisor while I finished up my own degree. They did the heavy lifting. I was paid for by F&A funds to do the boring work. Great job for a student.

The job lead to a failed business venture. Water under the bridge. My last foray in data analysis was Principal Component Analysis of the data, trying to cluster detected proteins for visual analysis. I got the plots working outside of Matlab, and then my position was eliminated.

I have a rag-mag credit I could chase down to support my war story. To be honest, I read the article looking for familiar names and faces.

None found.

I’m pretty sure this article is out of date, or at least the lab they interviewed is. The latest Bruker TOF quadrupole ion trap mass spec is able to sample (tens of?) thousands of ion or m/z datapoints per minute with an optional electrospray ionizer that can handle 100s of kilodaltons so that’s no longer the bottleneck for most proteomics. Actually discriminating charge ratios and data analysis now is.

However I don’t think many academic labs have those mass specs because CROs and pharmaceutical companies have been buying out Bruker’s entire production line and running them almost 24/7 to analyze samples from clinical trials. Since they’re limited in how much blood they can draw per patient, those mass specs significantly expand the number of analytes they can test for and they’re willing to pay serious money for that.

As noted above, I was working out of an academic lab developing new equipment. We had current-level commercial equipment at the time to use in comparisons. I matched data to the data dictionary, recovered backups, scripted backups, sent alerts to grad students that their results were done, maintained and expanded the visualization software, consulted and contributed code to a Monte Carlo simulation to demonstrate that data collected was better than random and by how much... Great little projects for a budding software developer. I had to learn just enough Chemistry and Physics beyond what I already knew to be dangerous (and also understand the what and why of what I was doing and be able to ask clarifying questions). It was fun.

There was quite a bit of fluff here so I only skimmed the article but the major takeaway here is that they figured out how to run protein mass-spec "by an order of magnitude" faster. This is certainly cool but I'm not sure I understand why this is on the front page of HN. What am I missing?

edit: Does anyone familiar with the field know what the significance of being able to run protein mass-spec an order of magnitude faster is? What kind of questions can we ask now that we couldn't ask before?

> I'm not sure I understand why this is on the front page of HN

Well, it's probably because `they figured out how to run protein mass-spec "by an order of magnitude" faster'.

OP isn't being dismissive, likely just skimming past the less essential details.

I guess a better way to put that would have been "what is the significance of being able to run protein mass-spec by an order of magnitude faster"

The article links this to Alzheimer's research but I was hoping someone on here familiar with the field would be able to point out how significant this advancement is.

Proteomics is the kind of fundamental research that can revolutionize every single area of medicine, biotech, and etc but is too central and general to have immediate applications on any specific thing.

I used to work in proteomics and I agree. The article is written at such a high level, the actual innovation is not that clear.

Barcodes that can 9 plex samples? Thermo TMT is up to 32 plex. Multiple injections with time offset? Also not a new idea.

What is unstated is that there is no free lunch. You can go fast or you can go “deep” (high resolution/separation). Running a MS at breakneck speed does work, but you are sacrificing quantitative accuracy and the depth of proteome coverage. Which is entirely valid way run, depending on your use case. Work in a hospital and need to do 1000 samples a day? Fast and targeted makes sense. Trying to discover some novel Alzheimer’s biomarker? You want to go slowly and measure everything you can.

Ultimately this is going to be just another tool available for researchers who have to weigh the pros and cons for the particulars of their samples.

The mention of PTMs was also a bit of a distraction. Measuring PTMs is an entirely different level of sophistication for which fast MS is rarely appropriate.

Edit: I should add that Alzheimer’s was probably just used as marketing copy, but is a terrible example for ludicrous-speed-go. Human Alzheimer’s samples are incredibly hard to procure. You either need brain or spinal fluid (apparently very painful to extract from the living). For precious samples you are usually willing to operate more slowly to ensure you do a better job.

On the other hand, there’s been some progress and proofs of concept regarding the use of nanopore technology for protein sequencing. Hopefully something useful comes out of it.

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