Sunday, September 1, 2019

There is still no convincing evidence for the frequent occurrence of posttranslationally spliced HLA-I peptides.

HLA peptides are the hottest thing to talk about in mass spectrometry in the US. There are probably 20 posts on this dumb blog about them demonstrating how little I know about them, and -- immunology in general...

Why they're important:
If you know the neoantigen things on the cell surface you can specifically target those cells for destruction. There have been some successes and many, many, many failures.

A recent hypothesis is very controversial, that part of the reason we can't figure it out is that during the protein processing in the whatever-its-called proteins are post-translationally spliced and kicked out.

Zach Rolfs et al., disagrees. This is the abstract. The entire abstract.

This short paper brings up a really important point. So important that I'll use both italics and bold again. Your database you use for both forward and decoy searches can massively influence the results of your proteomics search. I assume that most of the misguided souls who read this blog just rolled their eyes so hard at this last sentence that it hurt their ears. Yes. Obviously it does. However, have you seen an example as important as this?

There are people who are attempting to make antibody based drugs to target these peptides that are being demonstrated on the cell surface of cancer and other diseases.

This team goes to a previous study and reanalyzes the previous study's data with the same software using the same settings and all they do is change the way the FDR stuff is done.

And the results are completely different. The spliced peptides appear to disappear. Almost completely.

Which is right? The original study? The new re-analysis? Why would you ask a blogger?

What I do know? That biology shit looks hard. Last year I did hundreds of quality checks on antibody drug conjugates there is exactly one person there (who makes like $27k in an exploitation that the NIH is allowed to do that is called a "postbac") who ever sent an antibody that actually was what he was trying to make.

My assumption isn't that everyone else was dumb and useless, it was that you had to be really gifted to make antibody based drugs.

And if someone is going to pay a really gifted person $8 an hour to work on this -- we should manually review the data we send them least come up with a better and smarter way to do FDR on endogenous peptides! And this looks like a step in the right direction!

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