Tim O'Donnell

This is super helpful to know - thanks @jamieheather.bsky.social !

TCR-seq q: collaborator has ~10% of clones assigned to alleles IMGT says are "ORFs" like TRAJ44*01, TRBJ1-6*01 (this is 10x in mice). What can cause this? How likely are they productive TCRs? Maybe @jamieheather.bsky.social @victorgreiff.bsky.social @10xgenomics.bsky.social have ideas? 🙏

Newbie antibody design q: if I take a mouse IgG1 antibody and express its VH/VL on a human IgG1 constant framework, how likely is it to still bind the target? Does that kind of thing usually work?

I like how the deepseek r1 tech report includes an "ideas that didn't work" section (although it is admittedly very short). I wish more papers had that

Just got them now :)

Anyone receive the AF3 weights yet? (Applied on Mon, have not heard anything)

cc @alexr.bsky.social

Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress cancer immunotherapy - Nature Type 1 regulatory T cells (Tr1) represent a major obstacle that compromises naturally occurring and therapeutically induced tumour-specific immunity.

Missed this when it came out this summer - high doses of MHC II neoags in a peptide vaccine can be counterproductive due to a population of FOXP3− CD4+ regulatory cells that *kill* cDC1s. Big implications for peptide cancer vaccines if true www.nature.com/articles/s41...

This changed how I think about infectious disease - highly recommend www.annualreviews.org/content/jour...

I moved to Cambridge MA! If you're around and would like to meet up let me know. Looking forward to getting to know the community here

Say I have a deep learning model that runs on pairs of things M(a,b), and I want to distill it into three models X,Y,Z where Z(X(a), Y(b)) approximates M(a,b), and hopefully Z can be shallow and fast. Is that problem studied? What should I google?

Wow AlphaPulldown is great. Thank you!

Thanks! That looks helpful

Anyone know of a nice alphafold multimer batch inference script? I am doing an all against all run and would like to reuse MSAs etc. Running on an academic HPC cluster

Most memorable thing I've learned from #singlecellgenomicsday so far is from 2022... LIVE-SEQ does a "cytoplasmic biopsy" to profile RNA from a living cell without destroying it www.nature.com/articles/s41...

Thanks Kresten!

High quality benchmark of AlphaFold-Multimer and other tools on Ab/Ag complex structure prediction. Lots of room for improvement but the trope that AF can't do antibodies is not really right anymore after the late 2022 models update (v 2.3.0) www.biorxiv.org/content/10.1...

I love the simplicity of this idea - 1992 paper showing how to use FFTs to do rigid body molecular docking efficiently www.pnas.org/doi/abs/10.1...

Ok going to try using this. Who should I follow?