drug discovery researchers

Abstract: Can reflective language-model feedback improve a biological predictor when each cycle buys only one plate of labels? We separate three possible sources of benefit: proposing model edits, choosing measurements, and revising decisions through repeated feedback. We replay $36$ ProteinGym assays, starting with $96$ labels and acquiring $96$ per round for six rounds, with a sealed test set and a shared edit schema. The pre-specified comparison of full LLM control against random edits detects no advantage in test rank correlation ($Δz=-0.008$, $95\%$ CI $[-0.034,+0.018]$); equivalence is also unestablished. Exploratory ablations nevertheless identify useful model editing. With random acquisition fixed, LLM edits improve Fisher-transformed test Spearman by $0.043$ over no edits; with acquisition fixed to upper confidence bound, they improve normalized top-variant recovery by $0.023$. LLM acquisition alone does not detectably outperform fixed adaptive rules, and repeated feedback does not detectably outperform one initial recommendation under full control. Thus, the observed gains support constrained specialist editing, while the incremental value of recursive reflection remains unestablished at this label budget.

Abstract: Denoising Diffusion Probabilistic Models have emerged as powerful generative priors across domains ranging from molecular design to high-resolution image synthesis. However, standard diffusion sampling is inherently biased toward high-likelihood regions, often limiting the diversity of outputs. In many domains, a single, high-likelihood sample is insufficient. Instead, diverse portfolios of high-performing solutions are required, motivating methods that uncover a model's full expressive range. Here we show that integrating Quality-Diversity (QD) optimisation with diffusion models enables the discovery of diverse, high-performing outputs. We first propose Quality-Diversity Diffusion, a framework that adapts QD to diffusion models by directly optimising the model's latent noise and conditioning embeddings and leveraging embedding models to quantify diversity. Second, we introduce a novel h-space Spectral Mutation operator, which guides search along directions of maximal semantic sensitivity by analysing principal singular vectors of the model's input-to-activation Jacobian. We evaluate our combined approach, Spectral-Guided Quality-Diversity Diffusion, on text-to-image generation. Against 12 baselines, our method consistently achieves the lowest FID score, demonstrating an excellent balance of image quality and diversity.

Abstract: Over 90% of disease-associated variants from genome-wide association studies fall in noncoding regulatory regions, yet their functional interpretation remains a central open problem in genomic medicine. Large language models prompted to interpret such variants routinely hallucinate transcription factor (TF) binding changes, fabricate experimental support, and assign biological significance to statistically negligible signals. We present ARGUS (Agentic Regulatory Genomics for an Uncertainty-aware Scientist), which strictly separates deterministic biological computation from LLM-mediated reasoning. ARGUS wraps 458 DNABERT-based TF binding models in a hypothesis-directed investigation loop where a planner selects evidence sources based on current uncertainty, a verifier deterministically interprets each observation, and intermediate results change the investigation path. On variant rs6983267 at the 8q24 cancer risk locus, the same planner produces four divergent trajectories for four TFs. FOXA1 is rescued in 3 steps when real ADASTRA allele-specific binding data (15 experiments, FDR = 0.030) reveals a model false negative masked by saturation. KLF6 traverses 8 steps across ADASTRA, JASPAR motif analysis, and ENCODE cCRE regulatory annotation before abstaining due to mixed indirect evidence. RAD21 abstains in 8 steps after ADASTRA returns a coverage-qualified but nonsignificant allelic test (5 experiments, FDR = 0.65), and SP1, which shares FOXA1's saturated retained prediction, abstains because no direct experimental evidence exists at this locus. All observations come from real ADASTRA, JASPAR, and ENCODE cCRE queries; none are simulated. A comparison of fixed-priority and LLM-mediated planning shows that the LLM planner reaches identical verdicts with fewer tool calls by declining evidence that cannot resolve the claim under test.