Alex Rubinsteyn

Enumerating permutations and then cross-referencing them against the literature. A huge boost vs doing the same thing yourself!

Expanding the Unified Grammar for RNA Variants A unified toolkit for identifying and integrating DNA and RNA variants. Part 2 of the Neoantigen Discovery with Long-read Sequencing series.

open.substack.com/pub/pirlblog...

It’s not certain and can’t be done entirely in the world of bits but a path to inverting Eroom’s law is coming into view, fun time to be alive!

There are still missing steps in the world of atoms but some wins can come from unlocking scale on “platform” research reagents (eg mRNA too cheap to meter), some wins from flexible/personalizable therapeutic platforms (like neoAg vaccines but more general and actually effective)

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)

Thanks!

@tszzl.bsky.social on bsky?

Link to feeds and accounts please

The quality gap between ChatGPT5 Pro / Deep Research and R1 is just too big for anything open or local to be likely useful (sadly!)

Haven't tried consensus -- is open?

Tried FutureHouse tools ~2 months ago and found them still to be solidly in the "botslop" category

Walls of text that are superficially reasonable looking but don't help you learn anything (and sometimes actually fall apart logically upon inspection).

ChatGPT Pro & OpenAI's Deep Research are extremely useful for me wrt lit searches and do a decent but imperfect job at summarizing the salient themes in a pile of papers (the models are a bit too gullible and sometimes get obsessed with a niche idea from a random preprint). But it's still a huge win

I've been stuck in a bio knowledge containment field.

I generally have used ChatGPT more for science since Pro/Deep Research surface better papers and seem to summarize them more skeptically and faithfully.

But surprised that I can't get Claude to even answer simple things now

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

Light contamination in stable isotope-labelled internal peptide standards is frequent and a potential source of false discovery and quantitation error in proteomics - PubMed In mass spectrometry-based proteomics, heavy internal standards are used to validate target peptide detections and to calibrate peptide quantitation. Here, we report light contamination present in hea...

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?

Vaccine studies like to talk about their novel designs, cell therapies like to talk about their clinical responses

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

But if you want to effectively call the cops then you probably want a well staffed and funded police department…

(eg Durham has very wimpy response times to even serious gun crimes and so far many different calls to the police haven’t resulted in any action on the individual this thread is about)

I think you’re stating that last point a bit too strongly, I haven’t encountered anything like the ubiquitous US experience in much more culturally conservative countries. I suspect you’re, intentionally or not, only comparing with a handful of wealthy western countries

I do agree re: trying to nudge down the root causes of mentally unstable people in public and also agree that progressive policies might help in the long run.

But in the short run, you can’t just shrug these things off

I can definitely think of some policies to resolve this kind of situation but they seem very unprogressive (eg police foot patrols) — but it seems bad for “things that keep you and your family from getting killed by someone with stated homicidal intent” to be politically polarized

And we already have the HEART program in Durham.
The social workers have already been out to see him to no apparent effect.

The thing I’m struggling with is how do you violent anti-social people without leaving the fold of progressive politics.

I just can’t imagine any of that stuff being useful for this guy. He seems pretty content in his current routine (chasing joggers yelling “I’m going to kill you”)