Alejandro Lozano

ICML Conference 2025 Conference Paper

CellFlux: Simulating Cellular Morphology Changes via Flow Matching

• Yuhui Zhang
• Yuchang Su
• Chenyu Wang 0003
• Tianhong Li
• Zoe Wefers
• Jeffrey J. Nirschl
• James Burgess
• Daisy Ding

Building a virtual cell capable of accurately simulating cellular behaviors in silico has long been a dream in computational biology. We introduce CellFlux, an image-generative model that simulates cellular morphology changes induced by chemical and genetic perturbations using flow matching. Unlike prior methods, CellFlux models distribution-wise transformations from unperturbed to perturbed cell states, effectively distinguishing actual perturbation effects from experimental artifacts such as batch effects—a major challenge in biological data. Evaluated on chemical (BBBC021), genetic (RxRx1), and combined perturbation (JUMP) datasets, CellFlux generates biologically meaningful cell images that faithfully capture perturbation-specific morphological changes, achieving a 35% improvement in FID scores and a 12% increase in mode-of-action prediction accuracy over existing methods. Additionally, CellFlux enables continuous interpolation between cellular states, providing a potential tool for studying perturbation dynamics. These capabilities mark a significant step toward realizing virtual cell modeling for biomedical research. Project page: https: //yuhui-zh15. github. io/CellFlux/.

ICLR Conference 2025 Conference Paper

Time-to-Event Pretraining for 3D Medical Imaging

• Zepeng Huo
• Jason Alan Fries
• Alejandro Lozano
• Jeya Maria Jose Valanarasu
• Ethan Steinberg
• Louis Blankemeier
• Akshay S. Chaudhari
• Curtis Langlotz

With the rise of medical foundation models and the growing availability of imaging data, scalable pretraining techniques offer a promising way to identify imaging biomarkers predictive of future disease risk. While current self-supervised methods for 3D medical imaging models capture local structural features like organ morphology, they fail to link pixel biomarkers with long-term health outcomes due to a missing context problem. Current approaches lack the temporal context necessary to identify biomarkers correlated with disease progression, as they rely on supervision derived only from images and concurrent text descriptions. To address this, we introduce time-to-event pretraining, a pretraining framework for 3D medical imaging models that leverages large-scale temporal supervision from paired, longitudinal electronic health records (EHRs). Using a dataset of 18,945 CT scans (4.2 million 2D images) and time-to-event distributions across thousands of EHR-derived tasks, our method improves outcome prediction, achieving an average AUROC increase of 23.7% and a 29.4% gain in Harrell’s C-index across 8 benchmark tasks. Importantly, these gains are achieved without sacrificing diagnostic classification performance. This study lays the foundation for integrating longitudinal EHR and 3D imaging data to advance clinical risk prediction.

EAAI Journal 2025 Journal Article

Upper limb musculoskeletal model as path generator for control a virtual orthosis: A dynamic neural network approach

• Alejandro Lozano
• David Cruz-Ortiz
• Mariana Ballesteros
• Isaac Chairez

ICLR Conference 2025 Conference Paper

Video Action Differencing

• James Burgess
• Xiaohan Wang
• Yuhui Zhang
• Anita Rau
• Alejandro Lozano
• Lisa Dunlap
• Trevor Darrell
• Serena Yeung

How do two individuals differ when performing the same action? In this work, we introduce Video Action Differencing (VidDiff), the novel task of identifying subtle differences between videos of the same action, which has numerous applications, such as coaching and skill learning. To enable development on this new task, we first create VidDiffBench, a benchmark dataset containing 549 video pairs, with human annotations of 4,469 fine-grained action differences and 2,075 timestamps indicating where these differences occur. Our experiments demonstrate that VidDiffBench poses a significant challenge for state-of-the-art large multimodal models (LMMs), such as GPT-4o and Qwen2-VL. By analyzing the failure cases of LMMs on VidDiffBench, we highlight two key challenges for this task: localizing relevant sub-actions over two videos and fine-grained frame comparison. To overcome these, we propose the VidDiff method, an agentic workflow that breaks the task into three stages: action difference proposal, keyframe localization, and frame differencing, each stage utilizing specialized foundation models. To encourage future research in this new task, we release the benchmark and code.

AAAI Conference 2024 Conference Paper

MedAlign: A Clinician-Generated Dataset for Instruction Following with Electronic Medical Records

• Scott L. Fleming
• Alejandro Lozano
• William J. Haberkorn
• Jenelle A. Jindal
• Eduardo Reis
• Rahul Thapa
• Louis Blankemeier
• Julian Z. Genkins

The ability of large language models (LLMs) to follow natural language instructions with human-level fluency suggests many opportunities in healthcare to reduce administrative burden and improve quality of care. However, evaluating LLMs on realistic text generation tasks for healthcare remains challenging. Existing question answering datasets for electronic health record (EHR) data fail to capture the complexity of information needs and documentation burdens experienced by clinicians. To address these challenges, we introduce MedAlign, a benchmark dataset of 983 natural language instructions for EHR data. MedAlign is curated by 15 clinicians (7 specialities), includes clinician-written reference responses for 303 instructions, and provides 276 longitudinal EHRs for grounding instruction-response pairs. We used MedAlign to evaluate 6 general domain LLMs, having clinicians rank the accuracy and quality of each LLM response. We found high error rates, ranging from 35% (GPT-4) to 68% (MPT-7B-Instruct), and 8.3% drop in accuracy moving from 32k to 2k context lengths for GPT-4. Finally, we report correlations between clinician rankings and automated natural language generation metrics as a way to rank LLMs without human review. We make MedAlign available under a research data use agreement to enable LLM evaluations on tasks aligned with clinician needs and preferences.

NeurIPS Conference 2024 Conference Paper

Micro-Bench: A Microscopy Benchmark for Vision-Language Understanding

• Alejandro Lozano
• Jeffrey Nirschl
• James Burgess
• Sanket R. Gupte
• Yuhui Zhang
• Alyssa Unell
• Serena Yeung-Levy

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers’ efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs’ perception and cognition capabilities in biological image understanding. To address this gap, we introduce Micro-Bench, an expert-curated benchmark encompassing 24 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on Micro-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release Micro-Bench under a permissive license to accelerate the research and development of microscopy foundation models.