Wanyue Feng

Zhenyue Qin, Younjoon Chung, Elijah Lee et al.

Vision impairment affects millions globally, and early detection is critical to preventing irreversible vision loss. Ophthalmology workflows require clinicians to integrate medical images, structured clinical data, and free-text notes to determine disease severity and management, which is time-consuming and burdensome. Recent multimodal large language models (MLLMs) show promise, but existing general and medical MLLMs perform poorly in ophthalmology, and few ophthalmology-specific MLLMs are openly available. We present VOLMO (Versatile and Open Large Models for Ophthalmology), a model-agnostic, data-open framework for developing ophthalmology-specific MLLMs. VOLMO includes three stages: ophthalmology knowledge pretraining on 86,965 image-text pairs from 26,569 articles across 82 journals; domain task fine-tuning on 26,929 annotated instances spanning 12 eye conditions for disease screening and severity classification; and multi-step clinical reasoning on 913 patient case reports for assessment, planning, and follow-up care. Using this framework, we trained a compact 2B-parameter MLLM and compared it with strong baselines, including InternVL-2B, LLaVA-Med-7B, MedGemma-4B, MedGemma-27B, and RETFound. We evaluated these models on image description generation, disease screening and staging classification, and assessment-and-management generation, with additional manual review by two healthcare professionals and external validation on three independent cohorts for age-related macular degeneration and diabetic retinopathy. Across settings, VOLMO-2B consistently outperformed baselines, achieving stronger image description performance, an average F1 of 87.4% across 12 eye conditions, and higher scores in external validation.

Runmin Jiang, Genpei Zhang, Yuntian Yang et al. · cmu, harvard

Single-particle cryo-electron microscopy (cryo-EM) has become a cornerstone of structural biology, enabling near-atomic resolution analysis of macromolecules through advanced computational methods. However, the development of cryo-EM processing tools is constrained by the scarcity of high-quality annotated datasets. Synthetic data generation offers a promising alternative, but existing approaches lack thorough biophysical modeling of heterogeneity and fail to reproduce the complex noise observed in real imaging. To address these limitations, we present CryoCCD, a synthesis framework that unifies versatile biophysical modeling with the first conditional cycle-consistent diffusion model tailored for cryo-EM. The biophysical engine provides multi-functional generation capabilities to capture authentic biological organization, and the diffusion model is enhanced with cycle consistency and mask-guided contrastive learning to ensure realistic noise while preserving structural fidelity. Extensive experiments demonstrate that CryoCCD generates structurally faithful micrographs, enhances particle picking and pose estimation, as well as achieves superior performance over state-of-the-art baselines, while also generalizing effectively to held-out protein families.

Runmin Jiang, Wanyue Feng, Yuntian Yang et al. · cmu, harvard

Cryo-electron tomography (cryo-ET) enables in situ visualization of macromolecular structures, where subtomogram analysis tasks such as classification, alignment, and averaging are critical for structural determination. However, effective analysis is hindered by scarce annotations, severe noise, and poor generalization. To address these challenges, we take the first step towards foundation models for cryo-ET subtomograms. First, we introduce CryoEngine, a large-scale synthetic data generator that produces over 904k subtomograms from 452 particle classes for pretraining. Second, we design an Adaptive Phase Tokenization-enhanced Vision Transformer (APT-ViT), which incorporates adaptive phase tokenization as an equivariance-enhancing module that improves robustness to both geometric and semantic variations. Third, we introduce a Noise-Resilient Contrastive Learning (NRCL) strategy to stabilize representation learning under severe noise conditions. Evaluations across 24 synthetic and real datasets demonstrate state-of-the-art (SOTA) performance on all three major subtomogram tasks and strong generalization to unseen datasets, advancing scalable and robust subtomogram analysis in cryo-ET.