Identifiability Limits of Physics-Informed Inference for Spatial Stochastic Dynamics from Static Snapshots

Despite increasing scale and resolution, many biological measurements remain destructive, revealing only spatial information rather than the dynamics it encodes. By combining flexible representations with mechanistic constraints, physics-informed machine learning offers a promising route to inferring these dynamics from static snapshots. Motivated by subcellular imaging of gene expression, we ask when a static spatial pattern of molecules can identify spatially varying diffusivity, creation, destruction, and boundary exchange, and how different inference schemes perform on the task. A structural identifiability analysis shows that distributed sources are non-identifiable, whereas a point source such as a transcription site can restore identifiability. These limits are further shaped by seemingly innocuous modeling choices: the boundary conditions, the spatial regularity of the underlying dynamics, and even the stochastic calculus convention. We then adapt several physics-informed schemes, differing in how they represent the solution and enforce the governing equations, and demonstrate effective inference from a single snapshot. Physics-informed approaches can thus recover spatial heterogeneities of biological dynamics from static data, but their use should be accompanied and guided by careful identifiability analysis for meaningful interpretation of the results.

Maximum Matching Accuracy: An Instance Segmentation Evaluation Metric Utilizing Globally Optimal Matching

Reliable evaluation of instance segmentation models requires metrics that accurately and consistently reflect segmentation quality. However, the metrics most widely used in biological imaging carry fundamental mathematical weaknesses: hard Intersection-over-Union (IoU) thresholds that produce discontinuous, low sensitivity scoring; per-object normalization that distorts scores under object size variation; and greedy or one-to-many matching procedures that yield non-optimal, order-dependent correspondences. Together, these properties produce unintuitive and unreliable model rankings under common failure modes such as split cells, merged cells, and cell boundary imprecision. We propose Maximum Matching Accuracy (MMA), a threshold-free continuous metric that finds a globally optimal one-to-one matching between predicted and ground truth objects and aggregates total overlap using per-pixel normalization. We evaluate MMA against AP@50, PQ, SEG, and AJI across three experiments: synthetic failure cases, progressive corruption tests, and a model ranking comparison. MMA produces scores that are more stable, more sensitive, and more interpretable than existing alternatives, providing a principled foundation for fair instance segmentation benchmarking in biological cell imaging.

Assessing Sample Quality in Conditional Generation under Compositional Shift

Conditional generators provide a natural tool for controllable generation, including settings where the desired condition is a new composition of observed attributes or experimental factors. In many applications, especially in scientific domains, such models are attractive to explore conditions for which real samples are rare, expensive, or not yet observed. However, this creates a circularity for evaluation: standard conditional quality metrics require a reference target distribution, but in the extrapolative regime that distribution is unavailable by definition. We address this problem with a post-hoc, per-sample trust score for assessing conditional samples using only the training distribution. The score combines two estimable quantities: global realism, measuring compatibility with the real data manifold, and attribute-wise faithfulness, measuring whether a sample is closer to the requested attributes than to plausible alternatives. We show that the score can recover meaningful comparisons across extrapolated generations, under a mild coverage condition on the observed attributes. These comparisons enable effective filtering, ranking, and abstention of generations and can be used directly on off-the-shelf pretrained models. In biological imaging, selected samples preserve real morphological structure better and improve downstream predictive performance, while similar gains are observed on controlled vision benchmarks. Finally, we show how the score can be applied during generation, enabling abstention before full decoding. Code is available at https://github.com/berkerdemirel/faithful-cond-gen.