After a good bit of fighting with the code, I'm super excited to finally announce the release of my first ever app! AIMS - An Automated Immune Molecule Separator:

A great thread with some much needed testing of ML-based binding predictions! When AF3 can't fall back on its "secret sauce" of leveraging MSA for predictions, it shows just how far we are. Similar to the fundamental issues in TCR/Ab binding predictions. Excited for this paper!.

A great talk by Andreas, strongly recommend it to everyone interested in TCR specificity! Big takeaway for me is that we are quite a ways away from ML being useful in the specificity prediction problem given a random TCR. 99.99% of Andreas' new sequenced TCRs were orphans!.

I was invited to write a textbook chapter for "Methods in Molecular Biology: Immunoproteomics"! The final version will be behind a paywall, so here's a free copy. In it, I outline a step-by-step protocol for using AIMS to analyze immunopeptidomics data.

Recently been talking with a lot of people about the shortcomings of AI in biology, especially in T cell biology. Came across a decent summary of some of the issues today: A solid read! I recommend it, even if "crisis" is a bit strong.

Also, I'm really happy this was published in a journal where you can see the reviews and my responses. I think the 35 pages (!!!!) back and forth mostly with one unnamed, pugilistic, cantankerous reviewer really hammers home how robust this analysis is. Enjoy!.

However, thymic selection is also really important for determining the binding orientation! Biophysically, there's no reason TCRs can't dock on the MHC in a reverse orientation. This has been observed a few times, but is likely rare *because* of selection.

Basically, the germline encoded TCR CDR loops are far too variable for the previously proposed evolutionarily-conserved contacts to hold for all possible combinations of TCR-MHC. However, there is some clear signal of a (potentially) evolved "compatibility" between the two.

For decades, TCR-MHC interactions were thought of as arising through one of two frameworks; either as an evolutionarily conserved interaction, or as a consequence of thymic selection. My analysis suggests something of a middle ground. Both evolution and selection are important.

Really proud that this paper is finally out today in @eLife! I think a lot of the analysis in this paper can/should change the way we think about a really fundamental aspect of immunology: the interaction between TCRs and MHC.

My first publication as corresponding author is out today in its final form! I'm hoping this methods paper can essentially be the AIMS "bible". If you want to see how we can analyze TCRs, antibodies, peptides, and MHC all in one go, take a look:.

RT @CellReports: Biochemical and biophysical characterization of natural polyreactivity in antibodies

We don't think this is the *only* way you can get polyreactivity. And the field's ability to rigorously classify an antibody as "polyreactive" is still a bit shaky. But we think that these two manuscripts help open up some new ways of thinking about polyreactivity!.

This increase in inter- and intra-CDR loop interactions may work in two ways to create an "inoffensive" binding surface to a range of binding partners. First, it can sequester side chains and promote backbone interactions. Second, it reduces the entropic penalty to binding!.

In our bioinformatic analysis of thousands of sequences ( AIMS detected an increase in cross-CDR loop mutual information in polyreactive antibodies. This nicely matches with the increase in inter-loop hydrogen bonds seen in the new crystal structures.

In a somewhat counterintuitive finding, our results suggest that polyreactivity, at least in the antibodies we tested, can come about through a more rigid & flat binding interface. This is in contrast to previous results that suggest flexibility is key for poly Abs.

My last bit of graduate school-related work is out today in @CellReports ! . Some great experimental work by @mtborowska coupled with some MD simulations really nicely confirmed some of the AIMS predictions we previously published in eLife.

If you're interested in learning more about AIMS, check out the GitHub . Or my recent preprint highlighting the functionality of AIMS. (Which has been in review hell for quite a while, such is life).

Happy to announce a huge update to the AIMS software today! AIMS, which is used for analyzing TCR, antibody, peptide, and MHC sequences, can now be installed and run in two simple commands in a Mac/Linux terminal!. "pip install aims-immune"."aims-gui". Getting closer to AIMSv1.0!.

RT @ImmunityCP: New issue online! Cover depicts work from Esterházy, Brown, @macyrkomnick &co identifying lymph node co-drainage between pa….

RT @andimscience: The QImmuno Lab @iit_ucl @UCL_IPLS is hiring! 🥳 We have an opening for a fully funded PhD position (3 years) on physics-g….