Clay Kosonocky
@kosonocky.bsky.social
ML + Biochemistry PhD Candidate at UT Austin. BioML Society Founder. All problems are solvable, so let's solve some
biomlsociety.org
biomlsociety.org
Learn more at biomlsociety.org/challenge
September 2, 2025 at 2:45 PM
Learn more at biomlsociety.org/challenge
Huge shoutout to everyone that helped put on this event :)
Alex Abel, Aaron Feller, Amanda Cifuentes Rieffer, Phillip Woolley, Daryl Barth, Tynan Gardner , Wesley Wierson, Andrew Ellington, & Edward Marcotte (@edwardmarcotte.bsky.social)
Alex Abel, Aaron Feller, Amanda Cifuentes Rieffer, Phillip Woolley, Daryl Barth, Tynan Gardner , Wesley Wierson, Andrew Ellington, & Edward Marcotte (@edwardmarcotte.bsky.social)
September 2, 2025 at 2:45 PM
Huge shoutout to everyone that helped put on this event :)
Alex Abel, Aaron Feller, Amanda Cifuentes Rieffer, Phillip Woolley, Daryl Barth, Tynan Gardner , Wesley Wierson, Andrew Ellington, & Edward Marcotte (@edwardmarcotte.bsky.social)
Alex Abel, Aaron Feller, Amanda Cifuentes Rieffer, Phillip Woolley, Daryl Barth, Tynan Gardner , Wesley Wierson, Andrew Ellington, & Edward Marcotte (@edwardmarcotte.bsky.social)
We’re hoping to elucidate and share the trends in method choices to help our community hone in on standard practices for successful protein design :)
Stay tuned!
Stay tuned!
September 2, 2025 at 2:45 PM
We’re hoping to elucidate and share the trends in method choices to help our community hone in on standard practices for successful protein design :)
Stay tuned!
Stay tuned!
The full data release, scores, and analysis will be coming soon. We wish we could share all of the stats right now but we think it’s best if we release everything all at once when the publication hits preprint (hopefully in October!)
September 2, 2025 at 2:45 PM
The full data release, scores, and analysis will be coming soon. We wish we could share all of the stats right now but we think it’s best if we release everything all at once when the publication hits preprint (hopefully in October!)
Huge congrats to the winners! This is an absolutely mind-blowing feat and we can’t believe that designs from this competition worked so well. Each of the four winners will be given a 3D print of their winning binder, some stylish LEAH Labs swag, and, of course, bragging rights!
September 2, 2025 at 2:45 PM
Huge congrats to the winners! This is an absolutely mind-blowing feat and we can’t believe that designs from this competition worked so well. Each of the four winners will be given a 3D print of their winning binder, some stylish LEAH Labs swag, and, of course, bragging rights!
We’re also giving a second award to the team with the highest success rate of submitted sequences in the Round 1 screen. This team was Nucleate UK with a whopping 38% hit rate, with the runnerups being BindingIllini (15%) and Furman Lab (11%)
September 2, 2025 at 2:45 PM
We’re also giving a second award to the team with the highest success rate of submitted sequences in the Round 1 screen. This team was Nucleate UK with a whopping 38% hit rate, with the runnerups being BindingIllini (15%) and Furman Lab (11%)
Each design in the top ten succeeded at some aspect of T cell biology, but a few were successful in all of them! The teams with the top three designs were the Perez Lab Gators, Amigo Acids, and the Schoeder Lab. Each of these teams will be given an award 🥇
September 2, 2025 at 2:45 PM
Each design in the top ten succeeded at some aspect of T cell biology, but a few were successful in all of them! The teams with the top three designs were the Perez Lab Gators, Amigo Acids, and the Schoeder Lab. Each of these teams will be given an award 🥇
Round 2 (Individual Functional Assays)
The ten best performing sequences from Round 1 were selected to move on to a series of individual assays measuring many aspects of T cell biology including cytotoxicity against CD20+ tumors, cytokine release, proliferation, and expansion
The ten best performing sequences from Round 1 were selected to move on to a series of individual assays measuring many aspects of T cell biology including cytotoxicity against CD20+ tumors, cytokine release, proliferation, and expansion
September 2, 2025 at 2:45 PM
Round 2 (Individual Functional Assays)
The ten best performing sequences from Round 1 were selected to move on to a series of individual assays measuring many aspects of T cell biology including cytotoxicity against CD20+ tumors, cytokine release, proliferation, and expansion
The ten best performing sequences from Round 1 were selected to move on to a series of individual assays measuring many aspects of T cell biology including cytotoxicity against CD20+ tumors, cytokine release, proliferation, and expansion
This approach hijacks a necessary but not sufficient behavior of functional T cells—proliferation—to identify which binders engaged the antigen, signaled through their CAR, and became overrepresented at the population level
September 2, 2025 at 2:45 PM
This approach hijacks a necessary but not sufficient behavior of functional T cells—proliferation—to identify which binders engaged the antigen, signaled through their CAR, and became overrepresented at the population level
Round 1 (High-Throughput Screen)
The 12,000 CAR-T cell constructs were tested in a high-throughput pooled screen to measure how well the binders drove CAR-T cell proliferation in the presence of the target antigen CD20 compared to a control
The 12,000 CAR-T cell constructs were tested in a high-throughput pooled screen to measure how well the binders drove CAR-T cell proliferation in the presence of the target antigen CD20 compared to a control
September 2, 2025 at 2:45 PM
Round 1 (High-Throughput Screen)
The 12,000 CAR-T cell constructs were tested in a high-throughput pooled screen to measure how well the binders drove CAR-T cell proliferation in the presence of the target antigen CD20 compared to a control
The 12,000 CAR-T cell constructs were tested in a high-throughput pooled screen to measure how well the binders drove CAR-T cell proliferation in the presence of the target antigen CD20 compared to a control
The binders functioned in the context of CAR-T cells, serving as the binding domain that helps the CAR-T recognize the cancer antigen CD20. To validate them, we did two rounds of testing:
September 2, 2025 at 2:45 PM
The binders functioned in the context of CAR-T cells, serving as the binding domain that helps the CAR-T recognize the cancer antigen CD20. To validate them, we did two rounds of testing:
This was only possible thanks to LEAH Labs' high-throughput T cell engineering screen, DNA synthesis from
@twistbioscience.com, reagents from Lonza Group, ScaleReady, and VWR, and additional funding from the Center for Systems & Synthetic Biology at UT Austin
@twistbioscience.com, reagents from Lonza Group, ScaleReady, and VWR, and additional funding from the Center for Systems & Synthetic Biology at UT Austin
September 2, 2025 at 2:45 PM
This was only possible thanks to LEAH Labs' high-throughput T cell engineering screen, DNA synthesis from
@twistbioscience.com, reagents from Lonza Group, ScaleReady, and VWR, and additional funding from the Center for Systems & Synthetic Biology at UT Austin
@twistbioscience.com, reagents from Lonza Group, ScaleReady, and VWR, and additional funding from the Center for Systems & Synthetic Biology at UT Austin
We had 28 teams with competitors from 40 different countries design and submit a total of *12,000* peptide binders. All of the designs and methods, both in silico and in vitro, will be made public, and all parties agreed that no IP will be claimed to help further open science
September 2, 2025 at 2:45 PM
We had 28 teams with competitors from 40 different countries design and submit a total of *12,000* peptide binders. All of the designs and methods, both in silico and in vitro, will be made public, and all parties agreed that no IP will be claimed to help further open science
The methods used by scientists from *all over the world* resulted in antigen binders that plausibly act as cancer therapeutics. We can’t get over how cool this is!
September 2, 2025 at 2:45 PM
The methods used by scientists from *all over the world* resulted in antigen binders that plausibly act as cancer therapeutics. We can’t get over how cool this is!
Rather than test for just binding affinity, we tested these binders directly in the therapeutic modality to see how well AI protein design tools work towards a real-world scenario that could one day accelerate cell therapy prescription to days or weeks, rather than years
September 2, 2025 at 2:45 PM
Rather than test for just binding affinity, we tested these binders directly in the therapeutic modality to see how well AI protein design tools work towards a real-world scenario that could one day accelerate cell therapy prescription to days or weeks, rather than years
Perhaps this points to a need for non-anonymous online platforms with user ID verification and protocols to ensure content isn't AI-generated
We can still have our wild west anonymous internet, but IMO we also need a baseline of reality
We can still have our wild west anonymous internet, but IMO we also need a baseline of reality
May 17, 2025 at 2:18 PM
Perhaps this points to a need for non-anonymous online platforms with user ID verification and protocols to ensure content isn't AI-generated
We can still have our wild west anonymous internet, but IMO we also need a baseline of reality
We can still have our wild west anonymous internet, but IMO we also need a baseline of reality
On the other hand this policy *clearly* reinforces echo chambers. "Anyone or anything that conflicts with my worldview is fake"
May 17, 2025 at 2:18 PM
On the other hand this policy *clearly* reinforces echo chambers. "Anyone or anything that conflicts with my worldview is fake"
On one hand, this is good because it shifts the burden of responsibility away from actual humans and puts them in higher esteem than the background internet content. "Surely no human would say such a thing. Must be a bot or a human influenced by bots"
May 17, 2025 at 2:18 PM
On one hand, this is good because it shifts the burden of responsibility away from actual humans and puts them in higher esteem than the background internet content. "Surely no human would say such a thing. Must be a bot or a human influenced by bots"
That said, I'm very thankful to chaidiscovery for releasing their model for people to tinker with (it really is great overall). Open models allow us all to find the quirks, and in the end everyone benefits from having more superior tools 😎
February 12, 2025 at 5:34 PM
That said, I'm very thankful to chaidiscovery for releasing their model for people to tinker with (it really is great overall). Open models allow us all to find the quirks, and in the end everyone benefits from having more superior tools 😎
Now you must note (!) that this is just looking at the *confidences* between the various structures. This is not looking at the actual positioning. I did not check that here
Overall for most ligands there isn't a crazy difference, but the variability is, in fact, higher
Overall for most ligands there isn't a crazy difference, but the variability is, in fact, higher
February 12, 2025 at 5:34 PM
Now you must note (!) that this is just looking at the *confidences* between the various structures. This is not looking at the actual positioning. I did not check that here
Overall for most ligands there isn't a crazy difference, but the variability is, in fact, higher
Overall for most ligands there isn't a crazy difference, but the variability is, in fact, higher
And we see it more clearly in these plots.
Ideally if there were no effect, the experimental conditions (plots 2 & 3) would be as tight with the y=x as the 1st plot. But we can see that some ligands just don't behave as well
Ideally if there were no effect, the experimental conditions (plots 2 & 3) would be as tight with the y=x as the 1st plot. But we can see that some ligands just don't behave as well
February 12, 2025 at 5:34 PM
And we see it more clearly in these plots.
Ideally if there were no effect, the experimental conditions (plots 2 & 3) would be as tight with the y=x as the 1st plot. But we can see that some ligands just don't behave as well
Ideally if there were no effect, the experimental conditions (plots 2 & 3) would be as tight with the y=x as the 1st plot. But we can see that some ligands just don't behave as well