Alex Rubinsteyn
@alexr.bsky.social
personalized cancer immunotherapy = genomics + immunology + machine learning + oncology
(pirl.unc.edu)
(pirl.unc.edu)
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)?
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)
molecular profiling as input data for:
computational target selection ->
computational therapeutic design ->
computational safety screening ->
on demand manufacturing using commoditized modalities (DNA, RNA, peptides)
November 7, 2025 at 8:07 PM
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)?
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)
molecular profiling as input data for:
computational target selection ->
computational therapeutic design ->
computational safety screening ->
on demand manufacturing using commoditized modalities (DNA, RNA, peptides)
November 7, 2025 at 3:47 AM
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)
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
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
November 4, 2025 at 1:39 PM
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
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...)
(currently have slides with Onion-or-Not...)
November 4, 2025 at 12:09 PM
What's the funniest dataset to use in an intro ML lecture?
(currently have slides with Onion-or-Not...)
(currently have slides with Onion-or-Not...)
TIL: the guy who originally wrote L’ Chaim Stalin was later executed by Stalin
(still a banger)
(still a banger)
November 1, 2025 at 8:06 PM
TIL: the guy who originally wrote L’ Chaim Stalin was later executed by Stalin
(still a banger)
(still a banger)
Reposted by Alex Rubinsteyn
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.
@jdworkin.bsky.social offers a much more thoughtful approach.
How Much Should We Spend on Scientific Replication? | IFP
A data-driven framework for targeting replication funding where it matters most
ifp.org
October 31, 2025 at 7:40 PM
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.
@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"
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"
October 31, 2025 at 4:16 PM
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"
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 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)
October 31, 2025 at 2:23 PM
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 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)
youtu.be/MuZDEphRbes
My kids like this song and immediately started singing it
(Taking all recommendations)
L'chaim Stalin
YouTube video by Daniel Kahn & the Painted Bird - Topic
youtu.be
October 31, 2025 at 11:46 AM
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)
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
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
SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade - Nature
mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.
www.nature.com
October 30, 2025 at 3:35 PM
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
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...
Inner Emigration
YouTube video by Daniel Kahn & the Painted Bird - Topic
www.youtube.com
October 24, 2025 at 5:36 PM
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.
October 24, 2025 at 3:48 PM
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)
(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)
October 9, 2025 at 4:54 PM
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)
(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)
(1) Dishevelled
(2) Frizzled
(3) Pikachurin
(4) Sonic hedgehog
(other, post below)
October 7, 2025 at 4:33 PM
Which one is your favorite?
(1) Dishevelled
(2) Frizzled
(3) Pikachurin
(4) Sonic hedgehog
(other, post below)
(1) Dishevelled
(2) Frizzled
(3) Pikachurin
(4) Sonic hedgehog
(other, post below)
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.
September 26, 2025 at 2:20 PM
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?
September 26, 2025 at 11:09 AM
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
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
September 25, 2025 at 11:10 AM
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
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
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
September 25, 2025 at 9:00 AM
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
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/
pubmed.ncbi.nlm.nih.gov/35119480/
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...
pubmed.ncbi.nlm.nih.gov
September 25, 2025 at 1:17 AM
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/
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
Like, people want a nice lifestyles for their smallish families, take little risk, & often seem to have loose bonds to a greater community
September 24, 2025 at 1:37 PM
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
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)
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)
September 23, 2025 at 11:39 AM
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)
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?
September 22, 2025 at 4:05 PM
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”
September 22, 2025 at 12:48 PM
Listening to the newest TWiV with the heads of the European Society for Clinical Virology and ECDC, thinking “you’re the A team now”