MOSAIC: Modality-agnostic Spectral Alignment for Federated Image-level Weakly Supervised Tumor Segmentation under Client-specific Missing Modalities

Trustworthy multimodal fusion in clinical settings requires handling incomplete and heterogeneous modality subsets across institutions, where privacy constraints prohibit centralized data sharing. Federated learning (FL) mitigates data-sharing constraints but suffers from client-specific missing modalities, where institutions possess incomplete multimodal subsets, degrading fusion quality and segmentation performance. While FL and weak supervision have been studied separately, their joint use with image-level labels under heterogeneous missing modalities remains unaddressed. We propose \textbf{MOSAIC}, the first modality-agnostic federated framework for weakly supervised binary tumor segmentation under client-specific missing modalities. We introduce a client-specific modality-alignment module that fuses available channels into a shared latent space without prior knowledge of modality identity, a spectral prototype alignment loss that reconciles cross-client distribution shift using compact non-invertible frequency-domain statistics, and a dedicated federated refinement network that denoises the resulting CAM pseudo-labels into accurate masks, breaking the accuracy ceiling of weak supervision. Experiments on three multi-institutional brain tumor benchmarks (FeTS2022, BraTS-MEN, and BraTS-SSA) demonstrate significant improvements over all image, box, and point-supervised baselines, approaching fully supervised accuracy using only image-level labels and reaching 0.84 Dice on FeTS2022. Dynamic new client addition enables previously unseen institutions to join an already-trained federation within 0.01-0.04 Dice without retraining. Code is available at https://github.com/Tarun2201/MOSAIC.

PlantBGC: Transformer for Plant BGC Discovery via Label-Free Domain Adaptation and Weak Supervision

Plant biosynthetic gene clusters (BGCs) encode specialized-metabolite pathways, yet curated plant BGC labels remain scarce, hindering supervised discovery at genome scale. Existing plant BGC mining tools are largely signature- and rule-driven and do not fully leverage recent advances in contextual representation learning for modeling long-range domain context and controlling false positives under strong domain shift. We seek an AI-assisted workflow that narrows experimental search space by transferring supervision from well-annotated microbial BGCs to plant genomes. We present PlantBGC, representing genomes as ordered Pfam-domain sequences and learning BGC-likeness with an encoder-only Transformer trained on MIBiG microbial BGCs and adapted to plants via label-free masked language modeling. On microbial benchmarks, PlantBGC achieves token-level AUC = 0.988 (10-fold CV) and 0.979 (leave-class-out). On plants, adaptation improves known-BGC recovery on n = 34 curated loci under strict 100% coverage, increasing recovery from 29.4% to 67.6% and indicating more complete boundaries. GO/KEGG-derived weak supervision reduces proxy primary-like ratio by 48.40% (GO) and 45.20% (KEGG), with consistent per-species reductions (paired Wilcoxon p = 1.53e-5). Compared to plantiSMASH, PlantBGC yields more compact loci on matched regions (median length ratio = 0.278; 93.8% of pairs are shorter).

Open-Ended CT Volume Segmentation with Weak Supervision from Language

We introduce a method for training a text-conditioned segmentation model for CT scans, which combines voxel-level supervision with coarse but scalable slice-level supervision from reports. We extract, from a large database of scan-report pairs, descriptions of findings with indices of slices where those findings occur. We then finetune a general-purpose 2D image segmentation model, SAM3, with standard segmentation losses from strongly labeled data and with a slice-level classification loss from the extracted weak supervision. Our results on the ReXGroundingCT dataset illustrate that this strategy improves the segmentation dice score: from an 8% relative gain when there are 1000 fully labeled volumes to 22% when there are 250 fully labeled volumes.

Gradient-Based Latent Decomposition Reveals Mechanisms of Feature Degradation in Weakly Supervised Mammography

Weakly supervised hierarchical models exhibit a persistent asymmetry: coarse lesion-type features are preserved under reconstruction while fine-grained malignancy cues degrade---a pattern with direct consequences for the clinical reliability of breast cancer screening pipelines. We introduce gradient-based orthogonal latent decomposition for hierarchical Variational Autoencoders~(H-VAEs) to mechanistically explain this asymmetry. The latent space is partitioned into a task-aligned component~($z_1$), shaped by coarse supervisory gradients, and an orthogonal residual~($z_{\text{res}}$) capturing remaining representational capacity. On~3,550 mammographic Regions of Interest~(ROIs) from CBIS-DDSM, only~$\sim$4.4\% of latent magnitude aligns with supervisory gradients, leaving~$\sim$95.6\% in the orthogonal residual upon which fine-grained pathology prediction primarily depends. The model achieves Stage-1~AUC~0.866 and Stage 2~AUC~0.552, with a reconstruction stability gap of $Δ_{\text{diag}}=5\%$ ($p=0.005$) and a classification gap of $Δ_{\text{AUC}}=0.314$ ($p{<}0.001$). Latent ablation confirms that features for both tasks reside heavily in~$z_{\text{res}}$, structurally explaining why reconstruction degrades pathology stability disproportionately. Comparisons with Multi-Instance Learning~(MIL) and Multi-Task Learning~(MTL) confirm generalization across architectures and modalities. These findings reveal that in high-dimensional spaces, a single coarse supervisory signal isolates only a sparse 1D latent direction, forcing critical fine-grained features into the vulnerable residual subspace.

Spatially Grounded Concept Bottleneck Models for Trustworthy Breast Ultrasound Diagnosis

Concept Bottleneck Models provide interpretable-by-design predictions by mediating diagnosis through human-understandable concepts, but in medical imaging, their trustworthiness is often limited by the quality and granularity of available supervision. In particular, predicted concept activations can be driven by irrelevant regions, leading to spatially unfaithful explanations. We study a data-centric spatially grounded Concept Bottleneck Model (SG-CBM) that leverages coarse lesion delineations as weak supervision to encourage anatomically plausible concept evidence. For breast ultrasound, we derive two clinically motivated zones from each lesion mask: (i) an in-lesion region of interest for morphology-related concepts and (ii) a posterior acoustic band for posterior phenomena. We train concept maps using a grouped spatial grounding objective and preserve semantic faithfulness with a linear bottleneck classifier. Across five-fold stratified group cross-validation, the proposed SG-CBM improves diagnostic AUROC and concept macro-AUROC while markedly increasing spatial alignment of concept evidence. We also perform a Train-corrupt/Test-clean annotation-quality stress test to quantify the impact of supervision quality on diagnosis and spatial faithfulness. Overall, the results underscore the need for data-quality-aware supervision design and systematic trustworthiness validation for deployable healthcare AI systems.

Using binary silver labels in electronic health records-based computable phenotyping algorithms

Gold-standard phenotype labels are often unavailable at scale in electronic health record (EHR) studies because they require manual chart review. Weakly supervised phenotyping methods instead use silver-standard labels, such as diagnosis-code counts, natural language processing (NLP) mentions, medication indicators, or laboratory thresholds. PheNorm is widely used for this purpose, but its original formulation was designed for count-valued silver labels and relies on log transformation, utilization normalization, and Gaussian mixture modeling. These steps are not directly suited to binary silver labels, which are common and may be highly informative. We propose Binary PheNorm, an extension that uses binary silver labels directly in the corruption-and-regression denoising step and produces a continuous phenotype score without EM calibration. We also consider a lasso-regularized version for high-dimensional EHR settings and combined models using both binary and count labels. In simulations, Binary PheNorm achieved strong discrimination using binary labels alone and often improved performance when combined with count labels. In anaphylaxis, AUC increased from 0.793 for an epinephrine-mention indicator to 0.891-0.892 after Binary PheNorm. In acute pancreatitis, AUC increased from 0.736 for a lipase-threshold indicator to 0.805-0.819. These results support Binary PheNorm as a practical weakly supervised approach when informative binary silver labels are available.

Active Learning for Efficient Annotation of Surgical Videos with Weak Supervision

Precise spatial-temporal annotation of laparoscopic videos is time-consuming and requires expert knowledge. We propose a human-in-the-loop knowledge acquisition framework that combines active learning with dual-loss optimization to significantly reduce the annotation effort needed for automatic localization and segmentation of objects in the surgical field. Our method employs a foundation model to generate temporally consistent class activation maps (CAMs) from video using two complementary training objectives: a weak supervision loss on video-level tool presence labels for weakly annotated data, and an image-level mask loss on human-corrected annotations obtained through active learning. Rather than requiring dense pixel-level annotation upfront, our pipeline iteratively proposes pseudo-masks that guide the expert annotator to refine the knowledge previously captured by the model. We demonstrate that our framework reduces the effort of surgical video annotation by 50% by the end of training in comparison to fully manual annotation. Through eliminating the need for large, fully annotated datasets from the start, this framework enables scalability to the development of surgical tool segmentation models. This iterative human-in-the-loop refinement supports efficient knowledge acquisition with minimal expert input, providing a practical and deployable strategy for expanding tool segmentation to larger, more diverse datasets and real-world clinical settings.

OBBSeg: Irregular Lesion Segmentation under Oriented Bounding Box Annotations

Pixel-level annotation remains a major bottleneck in medical image segmentation, making weak supervision an attractive yet under-constrained alternative. We propose OBBSeg, an intermediate supervision paradigm guided by Oriented Bounding Boxes (OBBs) that bridges the gap between full and weak supervision. By jointly encoding spatial extent and orientation, OBBs provide compact geometric supervision that better aligns with elongated or anisotropic lesions, reducing the ambiguity of coarse box annotations. To mitigate the inherent rectangular bias of OBBs, we introduce a Mask-to-OBB loss, a differentiable formulation that enforces geometric consistency between predicted masks and OBB regions. Furthermore, we incorporate prompt-driven semantic guidance through two complementary modules-PAFE and DBFE-which enhance foreground representation and suppress background interference. Extensive experiments on 13 datasets across 5 imaging modalities show that OBBSeg not only outperforms existing weakly supervised methods but also achieves performance comparable to fully supervised approaches, demonstrating its potential for efficient and scalable medical image segmentation. The code is available at https://github.com/StarLxc3/OBBSeg.

Learning Where to Look: A Reinforcement Learning Framework for Robust Micro-Ultrasound Prostate Cancer Detection

Micro-ultrasound ($μ$US) is a new, emerging, and promising imaging modality for prostate cancer (PCa) detection, but accurate identification of suspicious tissue remains highly dependent on clinical experience, leading to substantial inter-observer variability. Machine-learning assistance can reduce this variability; however, training reliable deep models is challenging because supervision is sparse and noisy -- typically limited to core-level histopathology outcomes (e.g., cancer grade and its percentage in a biopsy core) without pixel-level lesion annotations and under severe class imbalance. We introduce Prost-RL, which reframes $μ$US PCa detection as a spatially aware, policy-driven inference problem by learning where to look before decoding. Prost-RL integrates a lightweight reinforcement-learning policy into a foundation-model encoder-decoder to generate interpretable spatial attention maps that act as soft prompts for both cancer-likelihood heatmap prediction and image-level classification. We further propose Adaptive Policy Optimization (APO) to stabilize hybrid supervised-RL training and a noise-robust objective combining symmetric cross-entropy with negative-entropy regularization to mitigate weak-label noise and encourage sharp localization. On a cohort of 6,607 biopsy cores from 693 patients across five clinical sites, Prost-RL achieves $79.0\pm3.5$ AUROC with $64.6\pm6.3$% sensitivity at 80% specificity for core-level detection (+2.1 AUROC and +4.5 sensitivity points over the strongest baseline), and $79.3\pm5.8$ AUROC for clinically significant cancer classification. The learned policy highlights biopsy-aligned regions, providing transparent, spatially grounded evidence alongside quantitative risk predictions. Code is available at: https://github.com/DeepRCL/Prost-RL.

Preference-based Antibody Expression Ranking: Scaling with Large-scale Weak Supervision

Antibody expression ranking is a critical task in antibody design, yet its modelling is severely hindered by the scarcity of labeled experimental data. To address this, we propose a unified preference-based learning framework that integrates scarce quantitative expression data with large-scale weak positive supervision from immunization data. We adapt Direct Preference Optimization (DPO) to protein language models by introducing a union-masked log-likelihood approximation and IMGT-based alignment, enabling efficient training on variable-length sequences. Evaluating on a diverse internal dataset of 1254 labeled sequences and 4 million unlabeled camelid-derived antibodies, we show that our method consistently outperforms baselines on most metrics. Our results demonstrate that preference learning can effectively learn from weak supervision, providing a scalable solution for antibody expressibility optimization in data-constrained settings. Project page: https://kisoji-biotechnology-inc.github.io/Preference-Expression-Ranking/.