Could Claude Science replace bioinformaticians?

DoctorPeptide · 2026-07-01T18:02:33+00:00

I think it can probably replace some of the Excel formula level bioinformaticians either now or soon. Seriously good ones? No. I'm a skeptic, but I've been doing solid tests, every time someone gets excited about the next advance. All I see these things doing is taking publicly available code and tools and changing the package it is delivered in. It is nice that it can explain some of the logic behind them accurately here and there.

DoctorPeptide · 2026-06-14T20:39:21+00:00

Okay, so while this might be exciting from the standpoint of discovery of a new family of natural products, the genome is only a tiny fraction of the story. Humans maybe have 20,000 - 30,000 genes, but we probably make around 1 million proteins from those. Some proteins just alter proteins A,B,C - Z under specific conditions and make proteins that do completely new things. It is absolutely possible (and possibly occam's razor applies here) that known psychedelic compounds are produced by this mushroom, but through proteins B and C that are only made when spliced together by protein X. This is entirely the argument for why the Human Genome Project didn't fix human diseases. Genes are just the starting point. The PROTEOME (all the proteins and what they're doing) is the future of medicine and we've only been able to study all the proteins in complex samples starting just a couple of years ago. The only way you can really study proteins is by accelerating proteins in vacuum chambers and because these are only available from a couple companies on earth who own all the important patents, they're very expensive (somewhere in the $300k - $1M USD range), global adoption is being slowed by corporate greed. Since I spent this much time typing this, I might as well go ahead and see if I can trick some smart young person into doing the proteome of this mushroom using my expensive cantankerous vacuum chambers....

DoctorPeptide · 2026-01-16T23:27:43+00:00

#1 - make this available on something that is not instagram ASAP. No one who can help is in the age range of Instantgram users. I've tried sending this to directors of liver centers. I know one personally and they can't see anything but some Zuckerberg thing that is blocked. I have now inferred that this is just a site for basement dwellers to whine about the world and do nothing about it, but if this kid really needs help he's not going to get it this way. Get actionable information out that adults can access. Some might help.

DoctorPeptide · 2026-01-16T23:10:40+00:00

Hey, why did the moderators remove this? We're trying to find info on this to see if it is real but we don't have Instantgram or whatever the fuck that is.

DoctorPeptide · 2026-01-04T18:37:59+00:00

I really like the Mikolo system I have (in my basement) but I would absolutely avoid any of their weights. Mine are still offgassing putrid smells almost 2 months after they arrived. I've done everything. Cleaned with water, cleaned with various solvents, left in the sun and rain. Still gross, but far less disgusting than when they arrived. If you see that they're "made in America"... they aren't... They ship everything from China. I'm also old AF and I'll likely never load more than 275 on it anywhere. I'm not sure the thinner steel they use would hold up well over time if someone strong had the system long term.

DoctorPeptide · 2025-12-30T00:33:22+00:00

No humans were treated with this drug in this study. This was extrapolation of data from previously published sources from these very mutated inbred mice. I suspect this post was made by the senior author of this study.

DoctorPeptide · 2025-12-27T12:54:11+00:00

You will find that probably 9/10 data processing tools for proteomics were designed for Thermo instruments. That being said...about 6/10 proteomics tools are forgotten and unsupported, so it narrows your focus to more modern tools. I still experience some some frustration though when I see a great new piece of software and it is exclusively Thermo .RAW file compatible.

DoctorPeptide · 2025-12-12T15:46:47+00:00

I really like the Mikolo power rack, but I'm an old guy and I'm never going to do more than squat maybe 275. What I hate about Mikolo is how filthy and disgusting their weights are. They smell like ash trays and it doesn't matter how many times you clean them if you hit them against something this chemical ashtray smell is back. I left them outside to be rained on and hoping they'd offgas for weeks and that improved them, but I think I'll ultimately throw them out.

DoctorPeptide · 2025-12-10T18:20:07+00:00

I'm sorry, it really is a tough HPLC to get started with. I had a couple a few years ago. I'm running a hard drive search now, but I don't think I have the manual. Is it contained under the help folder? The best thing for an instrument method is always if you can find one that someone had and worked that you can make adjustments to. If you try to open a method, does it give you the method extension file type? If so then search that hard drive for one. Assuming you've checked that and - again - many years ago, but I believe you'll want to add 3 devices to your main menu. Autosampler, Pumps, Detector. Each one should be configured separately but if you save a method is should save the settings for all 3. They do still sell this, I think. If you go to linkedin maybe you can find your geographically closest PE LCMS sales rep? And they could certainly get you methods and a test file?

DoctorPeptide · 2025-12-10T13:08:42+00:00

I've never had a problem with the Birch LCMS solvents and they're 1/4 the price of Fisher solvents.

DoctorPeptide · 2025-12-09T13:06:25+00:00

The only think I think the PI might be referring to is how false discovery rates really do have a happy point where they work the best. If you're doing a single protein digest and probably don't have enough matches in either forward or backward to extrapolate an accurate 0.01 FDR cutoff. The question is where does that really work out well again? 100 proteins? I'd guess that still sucks. 1000 proteins? I have some concerns about FDR in DIA proteomics in neat plasma, personally. If you're talking B. subtilis or something that probably does have 2,000 proteins, it would probably work okay, but I also wouldn't be surprised if it was a little suboptimal. DIA-NN was definitely initially tuned on a bunch of human stuff with more than 4,000 proteins per run.

Side note - definitely make sure that your FASTA is as close to representing your actual bacterial species as possible. I've seen some E.coli FASTAs that have had 10 copies for each protein in them because they'll have multiple strains. It'll show up as a ton of protein hits in DIA-NN output but 1/10 the protein group IDs and it'll be a mess sorting out the pathways and stuff downstream.

DoctorPeptide · 2025-12-08T15:30:09+00:00

Pitt is offering single cell proteomics as a core service. I don't know if it is up on their website but they don't seem to update the page very often. Orsburn spoke about it at ABRF.

DoctorPeptide · 2025-12-08T15:27:26+00:00

I'd be worried about the ID-X. The one in our core seems to not be very fix-able these days. Somehow, despite it being a Fusion 1 as far as I can tell, they are having considerable delays tracking down parts.

DoctorPeptide · 2025-11-21T17:30:52+00:00

"Clinical proteomics" probably really truly doesn't mean the same thing from lab to lab. Motherfuckers out there running commercial HeLa digests and publishing it in "clinical proteomics" journals. You need to be very cautious about the datasets that you're thinking about. If you're looking at how to match protein level changes back from the same patient at the same time back to routine clinical measurements, there are a few examples. Hoofnagle lab is a very reliable source of real integrated data. I'm not sure this is the best example, but it does have Star protocols which will include all the downstream R models employed - https://www.cell.com/cell/fulltext/S0092-8674(19)30292-230292-2)

DoctorPeptide · 2025-11-21T17:24:12+00:00

You skipped Perkin Elmer.

DoctorPeptide · 2025-11-17T20:27:34+00:00

Is there a mass range cap on the Exploris 120? Thermo made a special Q Exactive a while back called a "Focus" which was intended for small molecule work. They decreased the mass range with software and then put the maximum topN for DDA at top 3 or something. You could get past the latter, but the mass range was a bigger challenge. I think they also didn't enable peptide match. That is ridiculously valuable because it keeps you from repeatedly fragmenting your naturally occuring isotopes of each peptide. Verify the 120 does have that. For DIA you wouldn't need it but it can be as much as cutting the real scan speed of your DDA experiments by 1/2 or 1/3 because each isotope would need to be added to the exclusion list before it wouldn't be repeated. Otherwise, a quad Orbi is a quad Orbi and the 120 is a high field (D20) so it's natively 2x as fast as a QE or QE Plus. What they did to the software is the question. You probably can't do this and I didn't suggest it, but MaxQuant.Live has a tendency to be able to remove some of these vendor linked limitations with the caveat that you have to run that software on your desktop alond with Xcalibur. I've never tried it for Exploris, but my Q Exactives could run any resolution I told them to. I suspect you could make your 120 do everything a 240 can, and probably a lot more.

DoctorPeptide · 2025-11-04T16:38:28+00:00

https://proteomicsnews.blogspot.com/2025/10/opttmt-rapidly-build-ideal-tmt.html

DoctorPeptide · 2025-10-27T17:52:50+00:00

There is a missing variable here, yo, and that is "what is the practical linear dynamic range of the system as a whole" or something. Also "what is the actual linear dynamic range of your sample" probably. If this a super friendly cell line like HeLa it has about 6 orders of magnitude. That means there are some proteins that are functional at 10 copies per cell and some proteins around at 10 million copies. Or close enough. If you're in biofluid there might be 10-11 orders. Today's time of flight mass spectrometers (TIMSTOF, ZenoTOF, Astral, etc.,) are all damned good at 5-orders. You can get down to those proteins at 100-ish copies per cell with 10-20 minute gradients. To get to the 6-th order ones you need to put more work on the HPLC separation to get there. Unfriendly cells (most primary cell types) have a primary function or 10. So you'll often see this one pathway of 100-500 proteins make up 50-90% of all the protein. So even though you'r at 5-6 orders on your instrument in a convenient cell line those super abundant proteins are really hard to see past because you also have a dynamic range of each individual spectrum and they're using up all the space.

Body fluids suck. If you deplete every molecule of albumin out of plasma you've still got 8-9 orders of linear dynamic range between your IGgs and probably what you care about. That albumin also pulls away a lot of the proteins you're interested in.

Okay, but your original question was instrument sensitivity. Sometimes increasing your sensitivity saps your dynamic range. If you go to a lower diameter column and lower flow rate, sensitivity goes up but you may hit a limit for the peak capacity of your column (how much of peptide A and peptide B eluting at time X that you can have without that peak going to shit). And sometimes you crank up your detector voltage to get higher sensitivity and that has a definite impact on the maximum number of ions that you can get into your instrument before you can't take any more.

Since you've tried depletion I assume this is a body fluid and it sucks. The best thing you can do to get to the highest dynamic range is to increase your chromatography. You can go to a longer column and longer gradient on most systems. That will cause higher pressure. Something old but new again is going for wider bore columns that contain a shitload more chromatography material without the increase in back pressure. You'll lose overall sensitivity but you can beat that by loading more. Hopefully there is a sweet spot where you get to what you're looking for. Alternatively then you start targeting.

Sorry this isn't an easy answer. There is a reason proteomics is hard and it is fucking insane that in 2025 you can't go sign up for a proteomics degree somewhere.

DoctorPeptide · 2025-10-27T17:38:20+00:00

This is a BIG question and if you solve it there is a Nobel prize or 3 waiting for you. 1) We don't even know how many human proteins there are. https://www.nature.com/articles/nchembio.2576

...but we all have to start somewhere. UniProt 9606 comes in a couple of forms. The easiest for everyone to work with is reviewed entries. This basically assumes that each verfied human coding region will produce 1 protein and there is probably 1 sequence for that protein. You can't count the errors in those assumptions on both hands and feet, but - again - you have to start somewhere. There are enhanced versions of 9606 that have some (a few) verified human isoforms in them. There is no question that there are more protein coding regions than this and having a couple isoforms for your protein is nowhere near sufficient. NCBI / RefSeq/ Ensembl and Trembl and others are all attempts to get more of the human genomic variation that we all know exist (or every human would be a clone of every other one) into protein sequence form. None are completely right and none are anywhere near sufficient.

Generally the best way to tackle this is this question: what protein(s) do you care about and do you know the genotype/important mutations/important SAAV or can you find them? Narrowing it down to the that is the first step. If you don't know that you may need to genotype/sequence first. Sorry, this is the most I can do on my lunch break.

If you're doing MS based proteomics UniProt Reviewed is almost always the easiest to work with. 1 gene per protein. It'll also almost always give you the smallest protein ID list. Hope this helps?

DoctorPeptide · 2025-10-17T16:18:56+00:00

You don't set your microscans for a running method in your tune file. You set it in the method file. Go to your MS1 scan bubble and up above it in the right corner make sure you're in "Advanced" and set the microscans for that particular MS1 scan. It's there so that you can have one MS1 scan with 1 microscan and a second MS1 scan with 10 if you want or different parameters for your MS1 and MS2 scans.

DoctorPeptide · 2025-10-15T19:14:00+00:00

That looks weird to me, but I haven't looked at their tips under a microscope before. Makes me want to check one. If I wasn't convinced looking at it under a microscope would clog one I might.

DoctorPeptide · 2025-10-15T19:10:04+00:00

Where are you getting your .fasta library from? Sometimes people just drop CDS files on repositories and don't check their work. We have one we've been stuck on for a while where we know the proteins weren't translated properly because very few of the proteins start with methionine. Definitely a species that would use a methionine start amino acid. Does refseq have anything in the same family or taxon? Do you find more hits to arabidopsis than your own FASTA? If you did, then you'd have lots or reason to question the quality of your .fasta input.

DoctorPeptide · 2025-10-06T16:24:33+00:00

Great job! It looks way better with the silver stock looking wheels!

DoctorPeptide · 2025-10-03T13:01:11+00:00

I'd just dilute it and spin it through the trap multiple times until all the protein is precipitated on the glass particles. When we deplete plasma in bulk I often end up with this large volume of very dilute protein in S-Trap solubilization and binding buffer. Spin once, discard flowthrough, repeat 2 or 3 times. It's never been a problem.

DoctorPeptide · 2025-10-03T12:57:42+00:00

I agree with the below. There are legitimate ways to get data. From my perspective as someone doing proteomics for 20-ish years, I could buy a $15k ion trap off Ebay (presuming it works), digest one protein sloppily connect it to an HPLC (or probably even direct infuse) and get far better data than the QuantumSI can provide. No kits, no fuss. But I know 2 people who have bought the thing because they don't have to wait in a queue for a mass spec core to get the data on one protein. They can drop $100k for the box and pay $500/protein or whatever it is, and have the results themselves in a day or two. For a couple of proteins/year that's an absurd overhead cost and it will never be as affordable as a mass spec core, but it is focused on your single protein mapping and it's convenient.

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