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arXiv 2025年

作者： Huang, Yepeng Su, Xiaorui Ullanat, Varun Liang, Ivy Clegg, Lindsay Olabode, Damilola Ho, Nicholas John, Bino Gibbs, Megan Zitnik, Marinka Department of Biomedical Informatics Harvard Medical School BostonMA United States Program in Biological and Biomedical Sciences Harvard Medical School BostonMA United States Harvard College CambridgeMA United States Clinical Pharmacology and Quantitative Pharmacology Clinical Pharmacology & Safety Sciences R&D AstraZeneca GaithersburgMD United States Clinical Pharmacology and Quantitative Pharmacology Clinical Pharmacology & Safety Sciences R&D AstraZeneca WalthamMA United States Program in Computational Biology Carnegie Mellon University PittsburghPA United States Imaging and Data Analytics Clinical Pharmacology & Safety Sciences R&D AstraZeneca WalthamMA United States Kempner Institute for the Study of Natural and Artificial Intelligence Harvard University AllstonMA United States Broad Institute of MIT and Harvard CambridgeMA United States Harvard Data Science Initiative CambridgeMA United States

Predicting clinical outcomes from preclinical data is essential for identifying safe and effective drug combinations, reducing late-stage clinical failures, and accelerating the development of precision therapies. Current models rely on structural or target-based features to identify high-efficacy, low-toxicity drug combinations. However, these approaches fail to incorporate the multimodal data necessary for accurate, clinically-relevant predictions. Here, we introduce MADRIGAL, a multimodal AI model that learns from structural, pathway, cell viability, and transcriptomic data to predict drug combination effects across 953 clinical outcomes and 21,842 compounds, including combinations of approved drugs and novel compounds in development. MADRIGAL uses a transformer bottleneck module to unify preclinical drug data modalities while handling missing data during training and inference—a major challenge in multimodal learning. It outperforms single-modality methods and state-of-the-art models in predicting adverse drug interactions. MADRIGAL performs virtual screening of anticancer drug combinations and supports polypharmacy management for type II diabetes and metabolic dysfunction-associated steatohepatitis (MASH). It identifies transporter-mediated drug interactions. MADRIGAL predicts resmetirom, the first and only FDA-approved drug for MASH, among therapies with the most favorable safety profile. It supports personalized cancer therapy by integrating genomic profiles from cancer patients. Using primary acute myeloid leukemia samples and patient-derived xenograft models, it predicts the efficacy of personalized drug combinations. Integrating MADRIGAL with a large language model allows users to describe clinical outcomes in natural language, improving safety assessment by identifying potential adverse interactions and toxicity risks. MADRIGAL provides a multimodal approach for designing combination therapies with improved predictive accuracy and clinical relevance. Copy

关键词： Diseases

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On the combination of two visual cognition systems using combinatorial fusion

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Brain informatics 2015年第1期2卷 21-32页

作者： Batallones, Amy Sanchez, Kilby Mott, Brian Coffran, Cameron Frank Hsu, D. Laboratory of Informatics and Data Mining Department of Computer and Information Science Fordham University New YorkNY United States Program for the Human Environment The Rockefeller University New YorkNY United States

When combining decisions made by two separate visual cognition systems, statistical means such as simple average (M1) and weighted average (M2 and M3), incorporating the confidence level of each of these systems have been used. Although combination using these means can improve each of the individual systems, it is not known when and why this can happen. By extending a visual cognition system to become a scoring system based on each of the statistical means M1, M2, and M3 respectively, the problem of combining visual cognition systems is transformed to the problem of combining multiple scoring systems. In this paper, we examine the combined results in terms of performance and diversity using combinatorial fusion, and study the issue of when and why a combined system can be better than individual systems. A data set from an experiment with twelve trials is analyzed. The findings demonstrated that combination of two visual cognition systems, based on weighted means M2 or M3, can improve each of the individual systems only when both of them have relatively good performance and they are diverse. © 2015, The Author(s).

关键词： Decision making

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Mapping Emergency Medicine data to the Observational Medical Outcomes Partnership Common data Model: A Gap Analysis of the American College of Emergency Physicians Clinical Emergency data Registry

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JACEP Open 2025年第1期6卷 100016-100016页

作者： Cohen, Inessa Diao, Zihan Goyal, Pawan Gupta, Aarti Hawk, Kathryn Malcom, Bill Malicki, Caitlin Sharma, Dhruv Sweeney, Brian Weiner, Scott G. Venkatesh, Arjun Taylor, R. Andrew Department of Emergency Medicine Yale School of Medicine New Haven CT United States Section for Biomedical Informatics and Data Science Yale University School of Medicine New Haven CT United States Program of Computational Biology and Bioinformatics Yale University New Haven CT United States American College of Emergency Physicians Washington DC United States Department of Emergency Medicine Brigham and Women's Hospital Boston MA United States Center for Outcomes Research and Evaluation (CORE) Section of Cardiovascular Medicine Yale School of Medicine New Haven CT United States

Objectives: This study aims to conduct a gap analysis to determine the feasibility of mapping electronic health record data from the Clinical Emergency data Registry (CEDR) to the Observational Medical Outcomes Partnership Common data Model (OMOP-CDM). Methods: We employed a structured approach using a custom-built comparison matrix. This matrix facilitated the alignment of CEDR data fields with the corresponding elements in the OMOP-CDM schema. Each field was evaluated for compatibility, with categorization into 3 distinct types: direct matches, fields requiring transformation, and fields with no OMOP-CDM equivalent. The mapping process was informed by consultations with the Observational Health data sciences and informatics community forums and was guided by existing documentation and best practices in data harmonization. We performed descriptive analyses, quantifying the extent of direct matches and identifying the specific transformations needed for each CEDR-CDM field to ensure compliance with the OMOP-CDM model. Results: Our analysis indicates a high degree of compatibility between CEDR and OMOP, with over 90% (244/269) of CEDR fields being successfully mapped. Specifically, 173 fields had direct matches, whereas 71 required transformations. Challenges identified include addressing fields unique to CEDR with no OMOP-CDM equivalent and managing the transformations required for proper alignment. Conclusion: The OMOP-CDM presents a promising framework for standardizing emergency medicine data, thereby enhancing future query automation, analytics, and cross-institutional collaboration. Despite the potential challenges in capturing unique CEDR fields and addressing necessary transformations, most emergency department data can be standardized within the OMOP-CDM, fostering broader insights and applications in research and public health. © 2024 The Author(s)

关键词： databases electronic health records emergency service informatics opioid/adverse effects quality of health care registries

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Sex differences in proteomics of cardiovascular disease – Results from the Yale-CMD registry

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IJC Heart and Vasculature 2025年 58卷 101667-101667页

作者： Liu, Yihan Wang, Zuoheng Collins, Sean P. Testani, Jeffery Safdar, Basmah Program in Computational Biology & Biomedical informatics Yale University New Haven CT United States Department of Biostatistics Yale University School of Public Health New Haven CT United States Department of Biomedical Informatics & Data Science Yale University School of Medicine New Haven CT United States Department of Emergency Medicine Vanderbilt University Medical Center Veterans Affairs Tennessee Valley Healthcare System Geriatric Research Education and Clinical Center (GRECC) Nashville TN United States Section of Cardiovascular Medicine Department of Internal Medicine Yale University School of Medicine New Haven CT United States Department of Emergency Medicine Yale University School of Medicine New Haven CT United States

Aims This study assessed sex-specific proteomic profiles by cardiovascular disease (CVD) phenotype (coronary artery disease [CAD] vs coronary microvascular dysfunction [CMD]) and describe their role in sex-specific pathways. Methods: In a secondary biobank analysis of the Yale-CMD registry, adults with ischemic symptoms who underwent cardiac positron emission test/computed tomography were categorized as a) controls (normal coronary flow reserve (CFR) > 2 without perfusion defect or coronary calcification), b) having CMD (CFR < 2 without defect or calcification), or c) having CAD (known CAD or new perfusion defect). Using proximity extension assays (Olink® Explore 3072), we examined 2944 proteins. Differential protein expression was assessed using linear regression models, adjusting for age, race, body mass index, diabetes, dyslipidemia, hypertension, or smoking. Results: Of 190 patients, 91 provided blood samples (mean age, 56 years;66 %, females;48 %, controls;24 %, CAD;27 %, CMD). Among controls, 15 proteins showed sex differences (5 proteins upregulated in females, 10 in males;false discovery rate [FDR < 0.05]). Upregulated in CAD patients were FSHB in females and INSL3 and EDDM3B in males (FDR < 0.05). Among CMD patients, SCGB3A1 and HGFAC were higher in females;INSL3, SPINT3, EDDM3B, and KLK3 were higher in males (FDR < 0.05). Per pathway analysis, females showed upregulation of immune pathways in CAD and lipid and glucose metabolism pathways in CMD. Males showed upregulated endothelial regulation of blood flow in CAD and increased angiogenesis in CMD. Conclusions: Sex differences exist in the proteomic profiles of CAD and CMD patients, highlighting a need for precision medicine. © 2025

关键词： Coronary artery disease Coronary microvascular dysfunction Olink Precision medicine Proteomics Sex differences

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Uncertainty abounds, what now?

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science 2025年第6740期387卷 1261页

作者： Dov Greenbaum Mark Gerstein The reviewer is at the Zvi Meitar Institute for Legal Implications of Emerging Technologies The reviewer is at the Harry Radzyner Law School The reviewer is at the Dina Recanati School of Medicine Reichman University Herzliya Israel The reviewer is at the Department of Biomedical Informatics and Data Science The reviewer is at the Program in Computational Biology and Bioinformatics The reviewer is at the Department of Computer Science Yale University New Haven CT USA.

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Machine Learning and Deep Learning Techniques for Prediction and Diagnosis of Leptospirosis: Systematic Literature Review

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JMIR Medical informatics 2025年 13卷 e67859页

作者： Suhila Sawesi Arya Jadhav Bushra Rashrash Health Informatics and Bioinformatics Program College Of Computing Grand Valley State University 333 Michigan St. NE Grand Rapids MI United States Data Science College Of Computing Grand Valley State University Allendale MI United States Department of Biomedical Science College of Liberal Arts and Sciences Grand Valley State University Allendale MI United States

Background Leptospirosis, a zoonotic disease caused by Leptospira bacteria, continues to pose significant public health risks, particularly in tropical and subtropical regions. Objective This systematic review aimed to evaluate the application of machine learning (ML) and deep learning (DL) techniques in predicting and diagnosing leptospirosis, focusing on the most used algorithms, validation methods, data types, and performance metrics. Methods Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, Checklist for Critical Appraisal and data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS), and Prediction model Risk of Bias Assessment Tool (PROBAST) tools, we conducted a comprehensive review of studies applying ML and DL models for leptospirosis detection and prediction, examining algorithm performance, data sources, and validation approaches. Results Out of a total of 374 articles screened, 17 studies were included in the qualitative synthesis, representing approximately 4.5% of the initial pool. The review identified frequent use of algorithms such as support vector machines, artificial neural networks, decision trees, and convolutional neural networks (CNNs). Among the included studies, 88% (15/17) used traditional ML methods, and 24% (4/17) used DL techniques. Several models demonstrated high predictive performance, with reported accuracy rates ranging from 80% to 98%, notably with the U-Net CNN achieving 98.02% accuracy. However, public datasets were underused, with only 35% (6/17) of studies incorporating publicly available data sources; the majority (65%, 11/17) relied primarily on private datasets from hospitals, clinical records, or regional surveillance systems. Conclusions ML and DL techniques demonstrate potential for improving leptospirosis prediction and diagnosis, but future research should focus on using larger, more diverse datasets, adopting transfer learning strategies, and integratin

关键词： leptospirosis machine learning deep learning prediction models diagnosis artificial intelligence convolutional neural networks support vector machines transfer learning zoonotic diseases

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The spatial zonation of the murine placental vasculature is specified by epigenetic mechanisms

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Developmental Cell 2025年第10期60卷 1467-1482.e8页

作者： Gehrs, Stephanie Jakab, Moritz Gutjahr, Ewgenija Gu, Zuguang Weichenhan, Dieter Mallm, Jan-Philipp Mogler, Carolin Schlesner, Matthias Plass, Christoph Schlereth, Katharina Augustin, Hellmut G. Division of Vascular Oncology and Metastasis German Cancer Research Center (DKFZ) Heidelberg 69120 Germany European Center for Angioscience (ECAS) Medical Faculty Mannheim Heidelberg University Mannheim 68167 Germany Faculty of Biosciences Heidelberg University Heidelberg 69120 Germany Institute of Pathology University Clinic Heidelberg Heidelberg 69120 Germany Computational Oncology Group Molecular Precision Oncology Program National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg 69120 Germany Division of Cancer Epigenomics German Cancer Research Center (DKFZ) Heidelberg 69120 Germany Division of Chromatin Networks German Cancer Research Center (DKFZ) and Bioquant Heidelberg 69120 Germany Institute of Pathology TUM School of Medicine Technical University of Munich Munich 80333 Germany Biomedical Informatics Data Mining and Data Analytics Faculty of Applied Computer Science and Medical Faculty University of Augsburg Augsburg 86159 Germany

The labyrinthian fetoplacental capillary network is vital for proper nourishment of the developing embryo. Dysfunction of the maternal-fetal circulation is a primary cause of placental insufficiency. Here, we show that the spatial zonation of the murine placental labyrinth vasculature is controlled by flow-regulated epigenetic mechanisms. Spatiotemporal transcriptomic profiling identified a gradual change in the expression of epigenetic enzymes, including the de novo DNA methyltransferase 3a (DNMT3A). Loss of Dnmt3a resulted in DNA hypomethylation and perturbation of zonated placental gene expression. The resulting global DNA hypomethylation impaired the angiogenic capacity of endothelial cells. Global or endothelium-predominant deletion of Dnmt3a resulted in impaired placental vascularization and fetal growth retardation (FGR). Human placental endothelial gene expression profiling associated preeclampsia with reduced DNMT3A expression. Collectively, our study identified DMNT3A as critical methylome-regulator of placental endothelial gene expression and function with clinical implications for placental dysfunction, as it occurs during preeclampsia or FGR. © 2024 The Authors

关键词： angiogenesis DNA methylation DNMT3A epigenetic regulation growth retardation placental endothelium spatial zonation

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A Consensus Privacy Metrics Framework for Synthetic data

arXiv

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arXiv 2025年

作者： Pilgram, Lisa Dankar, Fida K. Drechsler, Jörg Elliot, Mark Domingo-Ferrer, Josep Francis, Paul Kantarcioglu, Murat Kong, Linglong Malin, Bradley Muralidhar, Krishnamurty Myles, Puja Prasser, Fabian Raisaro, Jean Louis Yan, Chao El Emam, Khaled School of Epidemiology and Public Health University of Ottawa ON Canada CHEO Research Institute ON Canada Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany Department for Statistical Methods Institute for Employment Research Nuernberg Germany Institute for Statistics Ludwig-Maximilians-Universität Munich Germany Joint Program in Survey Methodology University of Maryland United States The Cathie Marsh Institute Research School of Social Sciences University of Manchester Manchester United Kingdom Department of Computer Engineering and Mathematics Universitat Rovira i Virgili Catalonia Tarragona Spain Max Planck Institute for Software Systems Germany Department of Computer Science Virginia Tech United States Department of Mathematical and Statistical Sciences University of Alberta Alberta Canada Department of Biomedical Informatics Vanderbilt University Medical Center NashvilleTN United States Department of Biostatistics Vanderbilt University Medical Center NashvilleTN United States Department of Computer Science Vanderbilt University NashvilleTN United States Department of Marketing and Supply Chain Management University of Oklahoma Oklahoma United States Medicines and Healthcare products Regulatory Agency London United Kingdom Berlin Institute of Health at Charité Universitätsmedizin Berlin Medical Informatics Group Berlin Germany Biomedical Data Science Center University Hospital Lausanne Lausanne Switzerland

Synthetic data generation is one approach for sharing individual-level data. However, to meet legislative requirements, it is necessary to demonstrate that the individuals’ privacy is adequately protected. There is no consolidated standard for measuring privacy in synthetic data. Through an expert panel and consensus process, we developed a framework for evaluating privacy in synthetic data. Our findings indicate that current similarity metrics fail to measure identity disclosure, and their use is discouraged. For differentially private synthetic data, a privacy budget other than close to zero was not considered interpretable. There was consensus on the importance of membership and attribute disclosure, both of which involve inferring personal information about an individual without necessarily revealing their identity. The resultant framework provides precise recommendations for metrics that address these types of disclosures effectively. Our findings further present specific opportunities for future research that can help with widespread adoption of synthetic data. © 2025, CC BY.

关键词： Differential privacy

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MedRep: Medical Concept Representation for General Electronic Health Record Foundation Models

arXiv

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arXiv 2025年

作者： Kim, Junmo Lee, Namkyeong Kim, Jiwon Kim, Kwangsoo Interdisciplinary Program in Bioengineering Seoul National University Korea Republic of Dept. of Industrial and Systems Engineering KAIST Korea Republic of Interdisciplinary Program of Medical Informatics Seoul National University Korea Republic of Dept. of Transdisciplinary Medicine ICMIT Seoul National University Hospital Korea Republic of Center for Data Science Healthcare AI Research Institute Seoul National University Hospital Korea Republic of Dept. of Medicine College of Medicine Seoul National University Korea Republic of

Electronic health record (EHR) foundation models have been an area ripe for exploration with their improved performance in various medical tasks. Despite the rapid advances, there exists a fundamental limitation: Processing unseen medical codes out of the vocabulary. This problem limits the generality of EHR foundation models and the integration of models trained with different vocabularies. To deal with this problem, we propose MedRep for EHR foundation models based on the observational medical outcome partnership (OMOP) common data model (CDM), providing the integrated medical concept representations and the basic data augmentation strategy for patient trajectories. For concept representation learning, we enrich the information of each concept with a minimal definition through large language model (LLM) prompts and enhance the text-based representations through graph ontology of OMOP vocabulary. Trajectory augmentation randomly replaces selected concepts with other similar concepts that have closely related representations to let the model practice with the concepts out-of-vocabulary. Finally, we demonstrate that EHR foundation models trained with MedRep better maintain the prediction performance in external datasets. Our code implementation is publicly available at https://***/kicarussays/MedRep. Copyright © 2025, The Authors. All rights reserved.

关键词： Electronic health record

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ConvNeXt Model for Breast Cancer Image Classification 6

ConvNeXt Model for Breast Cancer Image Classification

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6th International Conference on Cybernetics and Intelligent System, ICORIS 2024

作者： Setiawan, Devin Karnyoto, Andrea Stevens Intan, Indo Pardamean, Bens Department of Electrical Engineering and Computer Science University of Kansas Lawrence United States Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta Indonesia Department of Informatics Engineering Universitas Dipa Makassar Makassar Indonesia Computer Science Department BINUS Graduate Program Computer Science Program Bina Nusantara University Jakarta Indonesia

ISBN: (纸本)9798331539603

Breast cancer is an occurrence of cancer that attacks breast tissue and is the most common cancer among women worldwide, affecting one in eight women. In this modern world, breast cancer image classification simplifies the process of analyzing, providing objective and accurate results. By leveraging machine learning algorithms and computer vision techniques, we developed breast cancer detection. The dataset is histopathology dataset from BreakHis and UNHAS Hospital. We chose the ConvNeXt-Tiny model then modified the classifier head as the proposed method. Before the dataset is processed by the model, we augment the images by applying random horizontal and vertical flips, adjustments to brightness, contrast, saturation, and hue using color jitter. The augmentation process simulates real-world variance and enhances the model's ability to generalize to unseen data. Our proposed model gained better performance (accuracy, F1-Score) results compared two other techniques to VGG16 and SVM. According to our experiments, the F1-Score for the ConvNeXt-Tiny model with classifier head modification is higher at 0.9516, than the gain for VGG16 at 0.9292, and the gain for the SVM at 0.83. © 2024 IEEE.

关键词： Lung cancer

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