Joint Flow Matching Enables Continuous Dose-Conditioned Cell Morphing

Generative modeling has shown increasing promise for predicting cellular perturbation effects under chemical compound treatments. Existing approaches either model perturbation as a distribution-to-distribution mapping without explicit concentration handling, or treat concentration as a discrete class label, precluding continuous dose control. We introduce a joint flow matching approach that simultaneously models cell latents and drug concentration via a dual-timestep formulation, enabling dose-conditioned single-cell morphing through the invertibility of flow matching. The joint formulation induces a monotonic dose-response geometry in latent space and additionally supports concentration estimation from cell morphology. As proof of concept, we further demonstrate generalization to an unseen dose held out during training. Empirically, our method achieves competitive or improved per-concentration metrics on two compounds compared with representative baselines, while enabling capabilities structurally unavailable to discrete-class methods.

Sparse Concept Channels in Frozen 3D CT Vision Encoders

Large vision-language models are becoming increasingly dominant in 3D medical image interpretation, but we rarely know <i>which</i> internal units encode clinical findings or <i>where</i> that information lives in the representation. We first study this on a 3D chest vision-language model (Pillar-0) by probing its frozen vision embeddings. We show that (i) each radiological finding is encoded by a <i>sparse</i> set of ~10 vision-encoder channels that match full-feature classification performance and far exceed a zero-shot text prompting; (ii) turning off the channels tied to one finding, that finding's score collapses while unrelated labels stay stable; and (iii) the same sparse probe <i>replicates</i> on an architecturally unrelated 3D abdominal VLM (Merlin) suggesting a general property of frozen medical encoders. Our training-free concept channel probe (CCP) method, paired with a corpus-derived report template, outperforms published CT-CHAT on clinical efficacy and NLG metrics (F1 0.549 vs. 0.184; BLEU 0.483 vs. 0.373) at 22x lower latency. Our results provide a clear, reproducible characterization of how frozen medical encoders represent findings, demonstrating direct applicability across models.

Generating Physically Consistent Molecules with Energy-Based Models

Molecules in equilibrium follow a Boltzmann distribution, making the underlying energy landscape a physically grounded modeling objective. However, such landscapes are difficult to learn from data and, once learned, hard to sample from. Diffusion and flow-matching models sidestep these difficulties by learning a time-conditional score or transport field between noise and data, losing the energy inductive bias in exchange for a more tractable training objective. We introduce EBMol, an energy-based model (EBM) that restores this inductive bias by learning an atom-additive scalar potential without explicit simulation during training. Our method employs a flow-inspired Restoring Field Matching objective to approximate the energy landscape. We adopt the Mirror-Langevin algorithm for sampling, enabling unified updates of atomic positions and types, and incorporate parallel tempering for inference-time compute scaling. EBMol is the first EBM for 3D molecular generation to achieve state-of-the-art performance on QM9 and GEOM-Drugs. Moreover, we show that the learned energy landscape serves as a principled quality metric for ranking and filtering configurations, and demonstrate controllable generation without retraining through shape-steered sampling via potential composition and zero-shot linker design.

Repurposing Protein Language Models for Latent Flow-Based Fitness Optimization

Protein fitness optimization is challenged by a vast combinatorial landscape where high-fitness variants are extremely sparse. Many current methods either underperform or require computationally expensive gradient-based sampling. We present CHASE, a framework that repurposes the evolutionary knowledge of pretrained protein language models by compressing their embeddings into a compact latent space. By training a conditional flow-matching model with classifier-free guidance, we enable the direct generation of high-fitness variants without predictor-based guidance during the ODE sampling steps. CHASE achieves state-of-the-art performance on AAV and GFP protein design benchmarks. Finally, we show that bootstrapping with synthetic data can further enhance performance in data-constrained settings.

A Variational Perspective on Generative Protein Fitness Optimization

The goal of protein fitness optimization is to discover new protein variants with enhanced fitness for a given use. The vast search space and the sparsely populated fitness landscape, along with the discrete nature of protein sequences, pose significant challenges when trying to determine the gradient towards configurations with higher fitness. We introduce Variational Latent Generative Protein Optimization (VLGPO), a variational perspective on fitness optimization. Our method embeds protein sequences in a continuous latent space to enable efficient sampling from the fitness distribution and combines a (learned) flow matching prior over sequence mutations with a fitness predictor to guide optimization towards sequences with high fitness. VLGPO achieves state-of-the-art results on two different protein benchmarks of varying complexity. Moreover, the variational design with explicit prior and likelihood functions offers a flexible plug-and-play framework that can be easily customized to suit various protein design tasks.

An Adaptively Inexact Method for Bilevel Learning Using Primal-Dual Style Differentiation

We consider a bilevel learning framework for learning linear operators. In this framework, the learnable parameters are optimized via a loss function that also depends on the minimizer of a convex optimization problem (denoted lower-level problem). We utilize an iterative algorithm called `piggyback' to compute the gradient of the loss and minimizer of the lower-level problem. Given that the lower-level problem is solved numerically, the loss function and thus its gradient can only be computed inexactly. To estimate the accuracy of the computed hypergradient, we derive an a-posteriori error bound, which provides guides for setting the tolerance for the lower-level problem, as well as the piggyback algorithm. To efficiently solve the upper-level optimization, we also propose an adaptive method for choosing a suitable step-size. To illustrate the proposed method, we consider a few learned regularizer problems, such as training an input-convex neural network.

Synthetic Augmentation for Anatomical Landmark Localization using DDPMs

Deep learning techniques for anatomical landmark localization (ALL) have shown great success, but their reliance on large annotated datasets remains a problem due to the tedious and costly nature of medical data acquisition and annotation. While traditional data augmentation, variational autoencoders (VAEs), and generative adversarial networks (GANs) have already been used to synthetically expand medical datasets, diffusion-based generative models have recently started to gain attention for their ability to generate high-quality synthetic images. In this study, we explore the use of denoising diffusion probabilistic models (DDPMs) for generating medical images and their corresponding heatmaps of landmarks to enhance the training of a supervised deep learning model for ALL. Our novel approach involves a DDPM with a 2-channel input, incorporating both the original medical image and its heatmap of annotated landmarks. We also propose a novel way to assess the quality of the generated images using a Markov Random Field (MRF) model for landmark matching and a Statistical Shape Model (SSM) to check landmark plausibility, before we evaluate the DDPM-augmented dataset in the context of an ALL task involving hand X-Rays.

FlowSDF: Flow Matching for Medical Image Segmentation Using Distance Transforms

Medical image segmentation is a crucial task that relies on the ability to accurately identify and isolate regions of interest in medical images. Thereby, generative approaches allow to capture the statistical properties of segmentation masks that are dependent on the respective structures. In this work we propose FlowSDF, an image-guided conditional flow matching framework to represent the signed distance function (SDF) leading to an implicit distribution of segmentation masks. The advantage of leveraging the SDF is a more natural distortion when compared to that of binary masks. By learning a vector field that is directly related to the probability path of a conditional distribution of SDFs, we can accurately sample from the distribution of segmentation masks, allowing for the evaluation of statistical quantities. Thus, this probabilistic representation allows for the generation of uncertainty maps represented by the variance, which can aid in further analysis and enhance the predictive robustness. We qualitatively and quantitatively illustrate competitive performance of the proposed method on a public nuclei and gland segmentation data set, highlighting its utility in medical image segmentation applications.

Score-Based Generative Models for Medical Image Segmentation using Signed Distance Functions

Medical image segmentation is a crucial task that relies on the ability to accurately identify and isolate regions of interest in images. Thereby, generative approaches allow to capture the statistical properties of segmentation masks that are dependent on the respective medical images. In this work we propose a conditional score-based generative modeling framework that leverages the signed distance function to represent an implicit and smoother distribution of segmentation masks. The score function of the conditional distribution of segmentation masks is learned in a conditional denoising process, which can be effectively used to generate accurate segmentation masks. Moreover, uncertainty maps can be generated, which can aid in further analysis and thus enhance the predictive robustness. We qualitatively and quantitatively illustrate competitive performance of the proposed method on a public nuclei and gland segmentation data set, highlighting its potential utility in medical image segmentation applications.