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ml-design-loops

Machine learning for laboratory biology, built evaluation-first. Three closed-loop systems that each decide what to do next and score the result against ground truth with an explicit quality gate. Everything runs sim-first and CPU-only; the wet-lab arm swaps to real instruments with a one-line backend change.

The common thread is the gate, not the model: acceptance criteria, calibrated uncertainty, and QC checkpoints that define what "correct" means before anything is promoted. That is the part that has to hold when a method leaves the lab that invented it.

Components

Each folder is self-contained and has its own README and requirements.

A closed-loop assay optimizer: a Gaussian-process world model of a low-input library-prep assay, multi-objective Bayesian optimization (ParEGO), and a split-conformal accept / reject / escalate QC gate with a coverage guarantee. Reaches a release-grade protocol in about 29 percent fewer experiments than random, and auto-decides roughly 79 percent of protocols at zero error while escalating the rest to the bench. sklearn / scipy, runs in about 20 seconds.

A protein language model design loop: ESM-2 zero-shot deep-mutational scanning (masked-marginal) plus simulated-annealing in-silico directed evolution over pseudo-log-likelihood. Runs on Apple MPS in about 15 seconds. The evaluation is a biology check: the model conserves the structural core and rates chromophore position 66 as substitutable, which is exactly where nature makes GFP color variants.

An agentic Design, Build, Test, Learn engine: ESM-2 proposes variants, a liquid handler STARlet builds and tests them (real PyLabRobot, with ODTC and Heater-Shaker), a Cytation 5 reads GFP brightness, and a per-mutation model closes the loop through a promotion gate. Sim-first; hardware is a one-line backend swap per instrument. The avGFP demo climbs to about 2x wild type and recovers a canonical brightener.

Running any component

cd <component>
python -m venv .venv && ./.venv/bin/pip install -r requirements.txt
./.venv/bin/python run_demo.py     # run_dbtl.py in autonomous-protein-design

House style

Figures use a shared style (vizstyle.py per component): Manrope, a pastel blue / green / purple palette, and thin black lines on white.

About

Closed-loop ML for biology: ESM-2 protein design by simulated annealing, Bayesian assay optimization with a split-conformal accept/reject/escalate gate, and an agentic design-build-test-learn engine driving a liquid handler. Sim-first, CPU-only.

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