Imagine programming protein, DNA, and RNA systems like you would...

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Imagine programming protein, DNA, and RNA systems like you would write computer code, or even by natural language prompting of an AI agent. @brianhie and team just made this a reality with Proto: a high-level programming language for generative biology.

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Proto works from four primitives: a sequence, some form of selective pressure as a constraint, random mutations as proposals, and optimization toward fitness. Nature has been running this loop via evolution for millions of years.

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The team rebuilt five published design campaigns in Proto: symmetric protein oligomers, de novo monomers, CRISPR-Cas loci, multi-kilobase chromatin accessibility, and antibody CDRs. The models and optimizers differ in each, but all run on the same four primitives.

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Proto can incorporate new models as they’re released. With AlphaGenome, the team designed introns with cell-line-specific splicing, validated in human cells, and combined models to build orthogonal promoter-repressor pairs.

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To generate promoter-repressor pairs, Proto’s pipeline composed general-purpose generative and structural models to solve for both protein-protein and protein-DNA interactions simultaneously.

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Proto also works with AI coding agents that write programs from natural language instructions. The team used this to specify hundreds of protein complexes across the human proteome, a multi-step signaling pathway, and a cancer-targeting lentiviral therapy.

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Proto is open-source and the team hopes it becomes the tool researchers reach for whenever a new biological AI model comes out, either to plug it in themselves or find out if it's already there: proto.evodesign.org/landing

Get started using Proto with co-authors @aditimerch, @dan_guo_, @bviggiano_13, and Lucas Brennan-Almaraz: youtu.be/8UnOrC_0jmo

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Check out the preprint: biorxiv.org/content/10.648…

Or go behind the scenes with the developers of Proto: arcinstitute.org/news/proto

Imagine programming protein, DNA, and RNA systems like you would...

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