SetFlow: Generating Structured Sets of Representations for Multiple Instance Learning

Data scarcity is a major bottleneck in medical Multiple Instance Learning (MIL), especially for rare diseases or expensive modalities. We introduce a statistically grounded patient augmentation approach that generates realistic patients directly in embedding space. Using Gaussian Mixture Models as a probabilistic clustering approach on pooled instance embeddings from all patients, our method learns disease-specific "recipes"-statistical distributions of instances across unsupervised clusters. New patients are then generated by sampling embeddings from clusters based on learned recipes. Unlike existing methods that require examples from all categories, our method can generate patients offline by re-mixing pooled embeddings. Generated patients are further selected based on uncertainty quantification to improve MIL performance. We evaluate our method across three clinically relevant scarcity scenarios: (i) cross-dataset transfer, where an entirely missing "healthy" class is generated using statistics from an external cohort; (ii) low-data regimes, where class sizes are extremely limited; and (iii) small-cohort non-image tasks, including single-cell RNA-seq and flow cytometry. Across all experiments, our method improves performance over baseline, often outperforming other bag-mixing strategies. Notably, in the missing-class scenario, a performance comparable to full-dataset training is achieved, demonstrating its potential for rare disease diagnostic and privacy-preserving patient augmentation. The code is available at https://github.com/marrlab/RECIPE

Multiple Instance Learning (MIL) addresses problems where supervision is available at the level of bags of instances and has been successfully applied in fields ranging from computational pathology to satellite imagery. Nevertheless, existing algorithms struggle in the low-label regime that characterizes many real-world applications. Flexible models overfit and rigid ones fail to adapt to the task at hand. We show that pretraining an in-context learner with a Perceiver-style architecture on synthetic data yields a model that can solve new tasks from a handful of labeled bags. At inference time, classification happens in a single forward pass and requires no gradient updates. We propose and investigate different synthetic data generators for bag-structured data and find that they capture complementary inductive biases. A model pretrained on a mixture of these generators inherits their per-task strengths and achieves the best average performance across twelve MIL benchmarks, outperforming supervised baselines that require task-specific training.

Modern foundation models provide highly expressive visual representations, yet adapting them to high-resolution medical imaging remains challenging due to limited annotations and weak supervision. Mammography, in particular, is characterized by large images, variable multi-view studies and predominantly breast-level labels, making end-to-end fine-tuning computationally expensive and often impractical. We propose Multiple Instance Learning on Precomputed Features (MIL-PF), a scalable framework that combines frozen foundation encoders with a lightweight MIL head for mammography classification. By precomputing the semantic representations and training only a small task-specific aggregation module (40k parameters), the method enables efficient experimentation and adaptation without retraining large backbones. The architecture explicitly models the global tissue context and the sparse local lesion signals through attention-based aggregation. MIL-PF achieves state-of-the-art classification performance at clinical scale while substantially reducing training complexity. We release the code for full reproducibility.