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Active Target Discovery under Uninformative Priors: The Power of Permanent and Transient Memory

NeurIPS 2025 · Probabilistic and scientific modeling › Molecules and proteins · approach: Prediction-powered and conformal inference · 0 citations (OpenAlex)

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Proposes EM-PTDM, an active target discovery method that works without domain prior samples by pairing a frozen pretrained diffusion model (permanent memory) with a lightweight Doob's h-transform module (transient memory) trained via an EM-style update.

Problem

Active target discovery under a strict query budget in partially observable environments where no domain-specific prior samples exist, so learned diffusion priors are uninformative.

Approach

Decomposes the posterior score into a frozen pretrained diffusion score (permanent memory) plus a learned Doob's h-transform correction (transient memory) trained with a denoising score-matching loss, updated with an EM-style procedure that claims monotonic improvement of expected log-evidence; sampling ranks cells by a combined exploration (posterior sample disagreement) and reward-weighted explo

Key results

Measured effects reported in the paper

What was changedWhereMeasuredEffect
Use EM-PTDM instead of the strongest baseline, Greedy-AdaptiveActive discovery of CS species with GG prior · CS species discovery, budgets 150, 200, and 250SR: 0.4061 -> 0.4983; 0.5067 -> 0.6495; 0.5567 -> 0.6989Helped
Use EM-PTDM instead of the strongest baseline, DiffATDOverhead object discovery with ImageNet prior · Overhead object discovery, budgets 250, 300, and 350SR: 0.5143 -> 0.5620; 0.6391 -> 0.7013; 0.7348 -> 0.8256Helped
Update permanent memory between consecutive tasks (ablation)EM-PTDM · Overhead object discovery with ImageNet prior, budgets 250, 300, and 350SR: 0.5620 -> 0.5859; 0.7013 -> 0.7194; 0.8256 -> 0.8461Helped
Add transient memory via the h-model (ablation)EM-PTDM posterior estimation · Novel ATD tasks from sparse early observationsL2 semantic dissimilarity to ground truthHelped
Update the h-model after every observation rather than after accumulating several observations (ablation)EM-PTDM h-model update scheduler · Toy experiment, early discovery phasePosterior sample stabilityHurt

Surprising findings

Limitations

Experimental setup

Datasets: iNaturalist DOTA ImageNet

Benchmarks: iNaturalist species distribution (CS vs GG prior) DOTA overhead objects with ImageNet prior

Metrics: success rate (SR) L2 semantic dissimilarity

Baselines: Random Search DiffATD Greedy-Adaptive

Builds on: DiffATD Doob's h-transform denoising score matching

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