• by Unknown
     Wow, there are a lot of liver diseases and we've got decent diagnostics for….well…liver damage…. that's about it. A small panel of liver damage markers finalized around the time Stan Lee and Jack Kirby went on a creative bender and wrote everything from the Fantastic Four, through Spiderman and the X-Man comics. I'm not kidding, there really has been almost zero forward movement in liver diagnostics since the 1960s. The liver protein panel was old when I was running them in the clinic in 2003. And it's still the same thing. Could top down proteomics be the answer? Given the current limits […]
  • by Unknown
    Timing on this one is a little unfortunate, because everyone has schedules, however, we're getting this science fiction sounding new toy and I'm happy to invite you to this webinar next week! Okay, so what if you could do live cell imaging and – not messing around  – dose your cells with a drug and then use machine learning tools to go and pick up the cells that meet your criteria. For example, what if I was growing a population of cells – on the instrument(!!) – in the presence of a KRAS inhibitor and then when that annoying subpopulation of […]
  • by Unknown
     This new preprint is so legit. Not only does it identify a pile of histone post-translational modifications I didn't know about, but it does it fast AND it justifies the chemistry that makes it happen. What if the reason that some of these PTMs aren't visible is that the modification neutralizes that peptide's ability to pick up a charge? Makes sense. A lot of the more awful PTMs do. But what if you could make them visible by adding a boring ol' tandem mass tag? Bonus points for the introduction of an enzyme I didn't know about with an amazing name:Stop, don't […]
  • by Unknown
    If you are like me and you have a PC in your office that your IT security people don't know about (shhh!)  that you just copy your RAW files to in case you need to look at an actual spectrum, do I have great news for you! As of a few months ago Thermo started embracing Windows 11! Check out this list! 
  • by Unknown
     Leaving this here so I don't lose it for another week because I am incapable of committing any of these author names to memory.You'd think it would be easy to find something written in the last couple of years that was about tissue-specific proteomics, right? You would be very very very wrong. I have 9 tabs open on just the PC I'm standing in front of in my house (wait. why am I here? I have a meeting in Oakland in like 30 minutes…? TYPE FAST!)In 8 of these papers, the authors who wrote it used the GTEX RNA DATA to […]
  • by Unknown
     In an interesting recent trend, everyone seems to be emphasizing how small of a cell that they can do single cell proteomics on. Do we have a new winner? No, Akos did single E.coli. Even if it was only like 25 proteins, that's clearly the winner for craziest tiny cell idea.But this group did PBMCs! How much protein is in a PBMC? 14 picograms! (These author's math, not mine). FOURTEEN? My group has recently struggled with some human immune cells… and from the TICs I was guessing we were starting with less than 50 picogram. FOURTEEN? Geez.How'd they get there? NanoPots. Ouch. Okay, so something […]
  • by LCMSmethodAdmin
     I was making slides for a class lecture and went down a long and windy rabbit hole on what we now know about the discrepancies between RNA and protein regulation. I landed on this one from 2022, and while it may seem like I'm rage baiting….I think it should go here anyway..Despite the title of this blog post we aren't firmly blamed for all the errors. Some error does exist in the mRNA measurements, but it's pretty clear that the disagreement in protein measurements between different studies is something that is worth thinking about. 
  • by Unknown
     Wooo! Okay, if your reading this in a first world country this won't apply all that much to you. In my country you can now spend $20k USD per year on private health insurance for yourself and if you actually need it someone will be very financially motivated to deny you coverage for pre-exisiting conditions.What if you could wear an accelerometer (I'm sure my wristwatch has one) and it could predict you might have a pile of different diseases? BOOM – pre-existing condition. 100% profit for the most profitable scam in my whole country! Science fiction? Or science fact? A bunch of people […]
  • by Unknown
     Okay, we all need more ways to look at the quality of our data, particularly before we send it out to collaborators who may do who-knows-what with it! Only one QC tool out there gives you retro visualization options! And it's this one!https://dia-nn-qc.streamlit.app/Load a DIA-NN file and choose 80s terminal or 90s webpage or just the boring regular thing. Who says you can't have a creative background while you're making sure you've got the correct number of scans/peak? Not me! 
  • by Unknown
     What a great month for method names already! Introducing the… …sequential single pot digestion and then sequential enrichment of the phospho- and glyco- proteome! I'm not entirely sure what all the advantages are of the Muppet method. The authors make it seem very streamlined, and I'm guessing that you can get away with less sample and sample loss by keeping things in the tubes, but early in they have to spend a lot of time diluting urea down to functional levels. If you want a lot of the details on how this is performed you'll need to go to page 28 in […]
  • by LCMSmethodAdmin
     YES! Okay, so this is may finally be the smart solution to something we tried (and probably just about everyone else) with the SCoPE-MS/ScoPE2 workflows.If you have a "carrier" "boost" "basil" or "oregonO" channel, why couldn't you load that thing with phospho-enriched samples (for example) instead of 200 cells or a a diluted perfectly digested pooled sample? The reason appears to be that your coisolated peptide (or junk) background ends up leading to a preposterous number of false discoveries. Remember that in these workflows your complete and total evidence for that peptide being there in single cells is just your […]
  • by Unknown
    This one took me a couple of rounds of putting it down and coming back to it later.It's a smart concept and a very nice thing to think about as proteomics becomes more trusted as a diagnostic. I think I first thought it was something that it isn't, and that's why I had such a conceptual problem with it. Obviously, I might still have it wrong, but this is how I'd describe it. What if you had a random patient come in and you could do global untargeted plasma proteomics on their sample? Not inside of a controlled cohort that you planned […]
  • by Unknown
     I'm tired of reading today, but I really want to get back to this cool paper.Really deep multi-proteomic type analysis looking for markers for why almost everyone has liver inflammation, but for some people it's a really bad thing that progresses to worse things.You've got secretion proteomics, and neat plasma and depleted plasma, and some SomaScan data from a related study that they used, and normalized, but don't go into much. They describe the statistics and provide the output data as an excel spreadsheet, which I very very much appreciate. Really nice super high speed targeted work (5 minute gradients […]
  • by Unknown
     Oh. This is really cool. I'm so glad that SCIEX is finally getting some traction with their super cool ZenoTOF hardware. The high speed high resolution mass spec world is really super competitive right now. You really can't make a bad choice (aside from Agilent, obviously – hey, I didn't tell them to abandon global proteomics instrument market -they're doing fine in their chosen niches) for getting amazing proteomics data.There is exactly one instrument out there that has big ass magnets inside it that forces charges onto your peptides for democratic fragmentation. I was supposed to evaluate a ZenoTOF for […]
  • by Unknown
     Are you ready for deep visual lipidomics? No? Okay what about normal spatial lipidomics with deep visual proteomics? The diagram pretty much shows what the paper did, but the co-registration of the spatial data from the laser capture microdissection work (now called deep visual proteomics, y'all, get on the hip terminology) to the lipidomics is a star. This does come from the very small but valuable bank of post-mortem human brain tissue in Baltimore that one of these authors definitely didn't steal from another facility. Lipidomics was at 50um resolution on a Bruker TOF I'm not familiar with, but they did both […]
  • by Unknown
     Big thanks to Matt MacDonald for sending this last night with a "Wow" as the total email content so that I got to sleep at like 1am after I felt like I'd finally gotten through it. Honestly, "wow" is still the correct word for it. Before I get into it, this is the paper. Single cell proteomics still feels new, but maybe I'm just old, but we're still learning what assumptions we need to make to get to real biological discovery. Something I argued for years was that I'd much rather have more cells than more coverage, but I think I've fallen headlong into […]
  • by Unknown
     I want to close this tab on my desktop so I can see other tabs. Direct link to the PDF. For real, I think this box is cheap. Like I've seen it second hand for less than an HPLC. Even if you needed to buy some expensive reagents, it could be a legit way to get yourself into the world of MS imaging…
  • by Unknown
     Backtracking this post, not sure how I forgot to put it here! 
  • by Unknown
     Another one I missed and am coming back to so I don't lose it and can finally close a tab or two! Figure B above at the very least could save you a ton of time over optimizing this yourself! Insanely useful. CRITICAL REMINDER – FragPipe is free for Academic use only! If you're not an academic, please play by the rules and get a license from Fragmatics!If you're an academic, I think you could use this whole thing! 
  • by Unknown
     Wait. SDS-PAGE has enough sensitivity for single cell proteomics?  Hmmmm…. It probably does….at least for high concentration band recognition…and it would provide some level of proteoform resolution. I'll be honest, I first thought "…that sounds slow and silly…" but the more I think about it the more I like having this around as a concept – or even a first pass.They use the migration patterns for their output and then use statistics that can tell different single cancer cells apart by those patterns….I don't know about the 3D imaging part, and it is a preprint, so grain of salt over your […]

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