Genetic circuit design remains a laborious, expert-driven process despite decades of progress in synthetic biology. We study this problem through code generation: models produce Python code in pysbol3 to construct genetic circuits in the Synthetic Biology Open Language (SBOL), a formal representation that supports automated verification. We introduce GenCircuit-RL, a reinforcement learning framework built around hierarchical verification rewards that decompose correctness into five levels, from code execution to task-specific topological checks, and a four-stage curriculum that shifts optimization pressure from code generation to functional reasoning. We also introduce SynBio-Reason, a benchmark of 4,753 circuits spanning six canonical circuit types and nine tasks from code repair to de novo design, with held-out biological parts for out-of-distribution evaluation. Hierarchical verification improves task success on functional reasoning tasks by 14 to 16 percentage points over binary rewards, and curriculum learning is required for strong design performance. The resulting models generate topologically correct circuits, generalize to novel biological parts, and rediscover canonical designs from the synthetic biology literature.
The design of biological systems is hindered by uncertainty arising from both intrinsic stochasticity of biomolecular reactions and variability across laboratory or experimental conditions. In this work, we present a sequential framework to optimize genetic circuits under both forms of uncertainty. By employing simulator models based on differential equations or Markov jump processes alongside a reinforcement learning (RL) policy-based approach, our method suggests experiments that adapt to unknown laboratory conditions while accounting for inherent stochasticity. While previous Bayesian methods address uncertainty through iterative experiment-inference-optimization cycles, they typically require computationally expensive inference and optimization steps after each experimental round, leading to delays. To overcome this bottleneck, we propose an amortized approach trained up-front across a distribution of possible uncertain parameters. This strategy sidesteps the need for explicit parameter inference during the design cycle, enabling immediate, observation-based adaptation. We demonstrate our framework on models for heterologous gene expression and a repressilator circuit, showing that it efficiently handles both molecular noise and cross-laboratory variability.
Michal Kobiela, Diego A. Oyarzún, Michael U. Gutmann
Reactive synthesis, the problem of automatically constructing a hardware circuit from a logical specification, is a long-standing challenge in formal verification. It is elusive for two reasons: It is algorithmically hard, and writing formal specifications by hand is notoriously difficult. In this paper, we tackle both sides of the problem. For the algorithmic side, we present a neuro-symbolic approach to reactive synthesis that couples large reasoning models with model checkers to iteratively repair a synthesized Verilog implementation via sound symbolic feedback. Our approach solves more benchmarks than the best dedicated tools in the annual synthesis competition and extends to constructing parameterized systems, a problem known to be undecidable. On the specification side, we introduce an autoformalization step that shifts the specification task from temporal logic to natural language by introducing a hand-authored dataset of natural-language specifications for evaluation. We demonstrate performance comparable to that of starting from formal specifications, establishing natural synthesis as a viable end-to-end workflow.
Frederik Schmitt, Matthias Cosler, Niklas Metzger +4
Reinforcement learning with verifiable rewards (RLVR) trains language models using programmatically checkable signals such as unit-test outcomes, enabling direct optimization for functional correctness in code generation. We conduct an empirical study of RLVR for Python code generation on the MBPP benchmark using two small models (Qwen3-0.6B and Llama3.2-1B) with LoRA fine-tuning. Across multiple reward formulations such as: unit-test-only rewards, static-analysis-only shaping via the Ruff linter, and a combined reward, we compare group-based policy optimization variants (GRPO and GSPO) and evaluate both functional correctness and behavioral diagnostics. In our experimental setting, RLVR improves pass@1 on MBPP test by up to 13 percentage points under proposed combined reward configuration. However, we find that reward shaping can induce systematic behavioral shifts: using only static-analysis penalties may bias the policy toward shorter completions that reduce lint errors without reliably improving functional correctness. In contrast, combined rewards mitigate this degeneration and yield more stable trade-offs between correctness and style constraints. Overall, our results highlight that RLVR effectiveness for code generation is highly sensitive to reward design and optimization granularity, and that diagnostics beyond pass@1, including generation length, Ruff severity profiles, and execution error types are useful for identifying failure modes.