SVC-Probe: A Framework for Evaluating Perturbation Generalization in Spatial Foundation-Model Embeddings

This work examines perturbation generalization in spatial foundation-model embeddings derived from fluorescence microscopy images. Although these models can discriminate drug conditions accurately, it remains unclear whether the learned representations reflect patterns consistent with expected perturbation axes that transfer across drugs. We introduce SVC-Probe, a perturbation-aware framework that combines Subcellular Embedding Atlas Stability, Mondrian Neighborhood Graphs, and a Foundation Model Perturbation Probe to assess embedding stability, neighborhood rewiring, and centroid prediction under drug treatment. Applied to the CM4AI MDA-MB-468 chemical-perturbation atlas comprising 462 antibody labels and SubCell 1536-dimensional embeddings, SVC-Probe demonstrates that 98.6% three-way condition accuracy does not correlate with reliable cross-drug prediction, with cosine similarity diminishing from 0.944 in-domain to 0.30 under leave-one-drug-out evaluation, constituting a two-drug stress test rather than a general benchmark. Null calibration indicates that raw residual-turnover coupling is largely influenced by generic embedding structure, whereas a drug-specific signal emerges under vorinostat and is consistent with chromatin-related reorganization. In contrast, the paclitaxel axis is not robustly reconstructed, likely due to sparse coverage of microtubule-associated proteins. Together, these results introduce and demonstrate a reusable diagnostic framework for stress-testing spatial virtual-cell representations and indicate that perturbation generalization may serve as a stricter and more informative benchmark than baseline condition discrimination.

A Zero-Shot Deep Image Prior Framework for Denoising and Deconvolution in Fluorescence Microscopy

Fluorescence microscopy images are degraded by noise and diffraction-induced blur, which compromise structural fidelity and limit quantitative analysis. Supervised deep learning methods achieve impressive restoration performance but require large-scale paired datasets that are difficult to obtain in practice. To address this issue, we propose SDIP, a zero-shot deep image prior (DIP) framework that sequentially performs denoising and deconvolution without external training data. An aSeqDIP-based module first suppresses noise while preserving fine structures through sequential autoencoding regularization. In the deconvolution stage, a wavelet-based background correction step is incorporated before the proposed RLG-DIP module performs artifact-reduced deconvolution. RLG-DIP uses the Richardson-Lucy deconvolution result as a physically consistent guidance prior, integrating the imaging model with the implicit prior of DIP to stabilize the ill-posed deconvolution process. Experiments on the BioSR dataset across multiple cellular structures demonstrate that SDIP improves both signal-to-noise ratio and resolution, achieving superior visual quality and improved quantitative performance on most evaluated structures. The proposed framework may also provide useful insights for designing physically guided DIP methods for other inverse problems.

Mitigating Measurement-Induced Training Instability in Hybrid Quantum Neural Networks for Protein Classification

Hybrid Quantum Neural Network (QNN) classifiers produce logits as expectation values of quantum measurement operators. For standard Pauli measurements, these outputs are intrinsically bounded to the interval [-1,1]. When such bounded logits are used directly with the cross-entropy loss applied to softmax-normalized logits for multi-class classification, the loss function operates in a regime of weak sensitivity to logit differences. As a consequence, parameter gradients are suppressed, leading to unstable optimization in variational quantum classifiers (VQCs). In this work, we identify this effect as measurement-induced logit contraction, a previously uncharacterized source of trainability degradation in hybrid QNNs. To address this limitation, we introduce a learnable scaling parameter, termed Quantum Measurement Temperature (QMT), which rescales quantum measurement outputs prior to the loss. Unlike post-hoc calibration, QMT acts during training and compensates for the physically imposed bounds on quantum measurement outputs. This rescaling increases gradient magnitude and variance, thereby improving loss sensitivity. The proposed mechanism is architecture-agnostic and does not modify the quantum ansatz, circuit depth, or measurement operators. Experiments on fluorescence microscopy images and a six-class variant of Fashion MNIST demonstrate that QMT consistently enhances logit separation, strengthens gradients, stabilizes training across random initializations, and improves classification accuracy, relative to unscaled measurement readouts. These results demonstrate that QMT enables stable and reliable training of hybrid QNNs for practical applications.

MTCurv: Deep learning for direct microtubule curvature mapping in noisy fluorescence microscopy images

Accurate quantification of the geometry of curvilinear biological structures is essential for understanding cellular mechanics and disease-related morphological alterations. Microtubule curvature is a key descriptor of filament rigidity and mechanical perturbations. However, reliable curvature extraction from fluorescence microscopy images remains challenging due to noise, low contrast, and partial filament visibility. Existing approaches rely on segmentation pipelines with pre or post-processing, which are highly sensitive to segmentation errors and often fail under adverse imaging conditions. In this work, we propose MTCurv, a deep learning framework for direct, segmenta-tion-free regression of microtubule curvature maps from noisy microscopy images. Leveraging a synthetic dataset with pixel-wise curvature annotations, we reformulated curvature estimation as a regression problem and adapted an attention-based residual U-Net. To reduce hallucinations and enforce spatial coherence, we introduced a gradient-aware loss combining Mean Squared Error with a gradient consistency term. Beyond model and loss design, we evaluated commonly used regression and image quality metrics, revealing that many perceptual and blind metrics are poorly suited for curvature estimation. Correlation-based metrics, particularly Spearman correlation, emerged as more reliable indicators of curvature prediction quality. Experiments on two datasets of increasing difficulty demonstrated that MTCurv accurately recovers local microtubule curvatures, even in the presence of background fluorescence. Ablation studies highlighted the contribution of both residual encoding and attention-based decoding. Overall, this work provides a practical tool for filament curvature analysis and methodological insights for geometry-aware regression in biomedical imaging. Datasets and code are made available.