Neil Thomas
@countablyfinite.bsky.social
Research Scientist; AI + Biology
thomas-a-neil.github.io
thomas-a-neil.github.io
Multiple Sequence Alignments (MSAs) were also powerful for zero-shot design! Without any assay data, and even without structure or large-scale pretraining, we were able to design improved NucB variants with as many as 9 mutations from the wildtype.
March 12, 2025 at 5:18 PM
Multiple Sequence Alignments (MSAs) were also powerful for zero-shot design! Without any assay data, and even without structure or large-scale pretraining, we were able to design improved NucB variants with as many as 9 mutations from the wildtype.
We found that in a head-to-head comparison of ML-guided design versus high-throughput directed evolution, our ML system could design higher activity variants, with lots more diversity!
March 12, 2025 at 5:18 PM
We found that in a head-to-head comparison of ML-guided design versus high-throughput directed evolution, our ML system could design higher activity variants, with lots more diversity!
How did we engineer NucB? We used a variety of methods, encapsulated in our “TeleProt” framework (which “teleports” past holes in the protein fitness landscape!) We balance evolutionary (VAEs) and assay-labeled data (CNNs) when designing libraries, and adjust as data accumulates
March 12, 2025 at 5:18 PM
How did we engineer NucB? We used a variety of methods, encapsulated in our “TeleProt” framework (which “teleports” past holes in the protein fitness landscape!) We balance evolutionary (VAEs) and assay-labeled data (CNNs) when designing libraries, and adjust as data accumulates
Our protein engineering target was NucB, an endonuclease that can break down biofilms and has potential as a treatment for chronic wounds. It is active at pH 9, but needs to be highly active at pH 7 to unlock its potential as a therapeutic.
March 12, 2025 at 5:18 PM
Our protein engineering target was NucB, an endonuclease that can break down biofilms and has potential as a treatment for chronic wounds. It is active at pH 9, but needs to be highly active at pH 7 to unlock its potential as a therapeutic.
How did we engineer NucB? We used a variety of methods, encapsulated in our “TeleProt” framework (which “teleports” past holes in the protein fitness landscape!) We balance evolutionary (VAEs) and assay-labeled data (CNNs) when designing libraries, and adjust as data accumulates
March 12, 2025 at 5:02 PM
How did we engineer NucB? We used a variety of methods, encapsulated in our “TeleProt” framework (which “teleports” past holes in the protein fitness landscape!) We balance evolutionary (VAEs) and assay-labeled data (CNNs) when designing libraries, and adjust as data accumulates
Our protein engineering target was NucB, an endonuclease that can break down biofilms and has potential as a treatment for chronic wounds. It is active at pH 9, but needs to be highly active at pH 7 to unlock its potential as a therapeutic.
March 12, 2025 at 5:02 PM
Our protein engineering target was NucB, an endonuclease that can break down biofilms and has potential as a treatment for chronic wounds. It is active at pH 9, but needs to be highly active at pH 7 to unlock its potential as a therapeutic.