Certifying when decision-time information justifies adaptive experimentation

Adaptive laboratories choose measurements during experiments, yet most methods begin after adaptation is permitted. We introduce Opportunity-aware Policy Authorization for Laboratories (\OPAL{}), a framework that decides whether adaptation should be enabled at all. \OPAL{} uses a precommitted contract to require non-trivial adaptation, controlled target risk and positive executed value after cost. We establish an impossibility boundary: source outcomes and unlabelled target covariates cannot uniformly support non-trivial authorization under unrestricted conditional outcome shift, and derive a target-calibrated recovery. Applied to an unseen 11,265-compound Cell Painting partition, the frozen gate selected 595 compounds, captured 384 positive opportunities and achieved strictly positive executed value under least-favourable completion; its 5.18\% false-activation upper bound remained below a 7.5\% limit. Among six methods, only \OPAL{} combined non-zero activation with this risk control. Locked pharmacogenomic and finite-campaign studies distinguish policy misalignment from non-certifiability, establishing authorization as a distinct layer for safe adaptive science.

Auditing Retrieval-Augmented LLM Hypotheses for Longitudinal Cell Painting Morphology

High-content morphological profiling (Cell Painting) yields sensitive, high-dimensional signatures of cellular state, but translating longitudinal morphology trajectories into interpretable biology remains difficult, especially for weak, chronic perturbations such as low-dose-rate ionizing radiation. Large language models (LLMs) can synthesize heterogeneous evidence into biological narratives, yet their scientific use requires quantitative auditing. We present an evaluation-first, retrieval-augmented interpretation framework for longitudinal Cell Painting morphology, applied to a 9-week RPE-1 time course across five dose rates (0.003--6.0 mGy/hr). Week-matched treated-control morphology deltas are combined with retrieved perturbation neighbors, pathway context, and literature evidence through stable evidence identifiers, enabling an LLM to generate structured, evidence-linked hypotheses that are hierarchically summarized while preserving provenance. We introduce two quantitative auditing tests: V1 citation validity, which verifies that cited evidence identifiers exist in the prompt, and V2 proxy-based morphology compatibility, which evaluates consistency between predicted biological processes and the most altered morphology features. In our experiments, V1 detected no invalid evidence references, while V2 showed meaningful morphology compatibility that increased with perturbation strength and was positively associated with an independent morphology drift summary. The framework produces auditable, falsifiable biological hypotheses, including an adaptive phenotype involving metabolic reprogramming and proteostatic stress at lower dose rates (0.003--0.3 mGy/hr). Current limitations include proxy-based evaluation and the lack of ground-truth mechanism labels.