Other than neoantigen vaccines, has any other process been in trials which chooses therapeutic sequences computationally & then uses quick commoditized manufacturing (DNA/RNA/peptides)? What about personalization through an assay (eg neoAg TCR-Ts, bacteriophage bank, n=1 ASOs)?

Automated medicine = molecular profiling as input data for: computational target selection -> computational therapeutic design -> computational safety screening -> on demand manufacturing using commoditized modalities (DNA, RNA, peptides)

Please expand this genre for me: Ekh Lyuli (by Psoy Korolenko et al & Rajtaraj) Daloy Politsey (by Rajtaraj but not other versions) L’chaim Stalin (by Psoy Korolenko et al) Man with a Hat (by the Klezmatics) This is all my kids want, not even other songs by the same artists

What's the funniest dataset to use in an intro ML lecture? (currently have slides with Onion-or-Not...)

TIL: the guy who originally wrote L’ Chaim Stalin was later executed by Stalin (still a banger)

I love asking the question: how much should be spent on scientific replication? When asked, I have suggested that 1-2% of a funding budget felt right. "Felt right" meaning no evidence basis other than intuition. @jdworkin.bsky.social offers a much more thoughtful approach.

Holy cow, what a difference switching from TCR-TCE to TCR-T seems to make... Went from "cool that this works at all but only at higher E:T, wonder if the surviving fraction of cells will acquire resistance" to "nuked everything from space at 1:1, leave no cancer cell alive"

Is the ZSA voyager any good? (I desperately don't want to configure or customize a keyboard in any way, but do want an ergonomic / joint friendly setup for working from a coffee shop)

I need a song in the style of L’chaim Stalin….that isn’t about Stalin youtu.be/MuZDEphRbes My kids like this song and immediately started singing it (Taking all recommendations)

I've been asked about this paper (www.nature.com/articles/s41...) enough times that I finally had to read it. The basic claim is that mRNA vaccines had huge synergistic benefit with checkpoint blockade against lung cancer melanoma. tl;dr it's glam-slop & everyone involved should be embarrassed

Good to post this every few months: www.youtube.com/watch?v=wh7d...

PIRL focused our efforts on flavors of TCR therapeutics for NUT carcinoma targeting CTA pMHCs and holy cow the synergistic effect of everyone working on broadly the same thing is amazing. New data every week, every experiment informing a greater understanding. This is awesome.

I’ve been skeptical about AGI = rapid medical progress but starting to believe a weak form of this (Researchers assisted by the better AIs can move much faster than before, discover far flung areas niches they wouldn’t have considered & get good initial params for experimental design)

Which one is your favorite? (1) Dishevelled (2) Frizzled (3) Pikachurin (4) Sonic hedgehog (other, post below)

@tszzl.bsky.social on bsky?

Tried going back to Claude today and it’s…totally useless for biomed? Got this for many different questions in a row but can eventually get an answer if I write a long shpiel about why it’s really safe to tell me about an IHC CRO.

When mRNA synthesis too cheap to meter?

tl;dr MS guide SRM: select specific precursor m/z, collide, measure specific fragment m/z PRM: select specific precursor, collide, record all fragments DDA: pass all precursors, measure m/z (MS1), select top N, PRM DIA: select evenly spaced windows of precursor m/z, PRM

Meta-analysis of observational studies is such a cursed genre of paper. eg Ahlqvist 2024 does a careful sibling analysis to show that apparent slight Tylenol:ASD risk is artifactual Baccarelli 2025 throws both the full confounded cohort and smaller sibling study in the blender

We (me and @benjamingvincent.bsky.social) naively assumed that heavy isotope labeled peptide synthesis for targeted MS was a solved problem. Wish I had read more before ordering so many contaminated peptides: pubmed.ncbi.nlm.nih.gov/35119480/

I wonder if the political “big moral circle” of us over-educated folks is compensating for the actuality of day to day white collar culture. Like, people want a nice lifestyles for their smallish families, take little risk, & often seem to have loose bonds to a greater community

Has anyone done MS peptidomics on FFPE samples? If so, how did they get it to work? (imagine PRM gets thrown off by modified residues and DDA acquires too many bits of junk to make sense of original sequences)

Which New Year did early Israelites (ca ~1000BC) observe first: Spring or Fall?

Listening to the newest TWiV with the heads of the European Society for Clinical Virology and ECDC, thinking “you’re the A team now”

Is the 1939 recording of “Jane-Jane (Three mocking birds)” online anywhere? (Library of Congress has a photo of the card but not the actual audio)

Very preliminary figure from Steve Vensko in our lab but still wanted to share it. % melanoma patient samples (n=27) expressing CTA vs. % cells in non-zero samples expressing the CTA

My co-worker has stopped walking on the river trail between our houses bc of this guy: www.reddit.com/r/bullcity/s... He's internet-famous bc of how many people have been chased or threatened by him. Posting on bsky since I'm curious if there's any "progressive" solution to situations like this

Is there something wrong with the HLA-II entries of the HLA Ligand Atlas? Looked up the model PRAME epitope A2/SLLQHLIGL and found it's mostly detected on HLA-II alleles -- which doesn't make sense of a teeny little 9mer. (it's also weird to see it so much on healthy samples)

Hominid re-diversification

Was curious about the "Chinese peptides" phenomenon: asked someone on reddit, directed me to telegram, got a link to a source selling "retatrutide" -- but the info sheet had a molecular formula that didn't match the PubChem entry: pubchem.ncbi.nlm.nih.gov/compound/Ret... Be careful?

TWiV #100 with David Baltimore is excellent: podcasts.apple.com/us/podcast/t...

Elementary schools teach non-commutative integer multiplication!?

I regret to inform you that the Dwarkesh longevity episode is pretty good. I’m skeptical of TF therapies for de-aging and virtual cell models but the higher level conversation is interesting and scientifically grounded, he asks many good questions. Sorry.

Thinking about running a TCR generation contest: We give you a set of pMHCs without known cognate TCRs You give us your top k in silico TCR designs We test them for cytotoxicity as TCR-Ts against cancer cells that are validated to express the target Who’s in?

Not an accident that RNA polymerase sub-units ended up in the MHC locus (I suspect this is key to making the whole surveillance magic work)

George Bernard Shaw's (!) description of opsonization in 1906: "[...] phagocytes, which attack and devour disease germs for us, do their work only when we butter the disease germs appetizingly for them with a natural sauce [...]" – from his play The Doctor's Dilemma.

I think most people born in the US assume its stability at a very fundamental level. But if you come from a country that collapsed and/or are closely connected to family histories of violence and disruption, it’s hard to feel at ease. Always waiting for the other shoe to drop.

tl;dr T5 style translation model to generate T cell receptors from targets actually kinda works Caveats: not full TCR (CDR3b), strong signal that public data biased towards “polyspecific” TCRs — lo and behold, generated TCR-T is polyspecific in vitro. Open weights, go wild.

This is a cool story that I've watched with great interest - making big steps in the field of de novo TCR generation! Great work @dkarthikey1.bsky.social / @benjamingvincent.bsky.social / @alexr.bsky.social et al

Are there any promising WNV vaccines?

Last year's NUT Carcinoma Symposium was my favorite kind of workshop-style meeting w/ high density of research conversations. One outcome was formation of a new foundation (NUT Carcinoma Alliance), who are sponsoring another symposium! Tentative dates: March 18th & 19th 2026

Sad to report that the engagement gap between Twitter and bsky for technical posts keeps growing more severe I know that lots of scientists are here in theory…

Listening to my first Dwarkesh episode and…it’s pretty good? Definitely a funny sub-culture of jargon, vocab, & priorities but it’s fun to dream big

Recently tested some de-novo minibinders against two targets (thanks Adaptyv!) designed using our open-source design library, `mosaic`; our best method got hit rates of 7/10 and 8/10 and affinities as low as single-digit nanomolar. Wrote up some thoughts here: blog.escalante.bio/minibinder-d...

Curious what folks who work on iPSCs think of the @openai x @RetroBio_ [*] collab to design efficient Yamanaka factors using a fine-tuned GPT-4o. I wonder to what degree the designs integrate all the previously published work on sequence properties of improved Sox/Klf proteins

ban the internet, it's time. the only thing to exist is html and ascii geocities websites. we will be happier, and our websites will be beautifully bauhausian