Alex Bui

David Gordon, Panayiotis Petousis, Anders O. Garlid et al.

Several algorithms for learning the structure of dynamic Bayesian networks (DBNs) require an a priori ordering of variables, which influences the determined graph topology. However, it is often unclear how to determine this order if feature importance is unknown, especially as an exhaustive search is usually impractical. In this paper, we introduce Ranking Approaches for Unknown Structures (RAUS), an automated framework to systematically inform variable ordering and learn networks end-to-end. RAUS leverages existing statistical methods (Cramers V, chi-squared test, and information gain) to compare variable ordering, resultant generated network topologies, and DBN performance. RAUS enables end-users with limited DBN expertise to implement models via command line interface. We evaluate RAUS on the task of predicting impending acute kidney injury (AKI) from inpatient clinical laboratory data. Longitudinal observations from 67,460 patients were collected from our electronic health record (EHR) and Kidney Disease Improving Global Outcomes (KDIGO) criteria were then applied to define AKI events. RAUS learns multiple DBNs simultaneously to predict a future AKI event at different time points (i.e., 24-, 48-, 72-hours in advance of AKI). We also compared the results of the learned AKI prediction models and variable orderings to baseline techniques (logistic regression, random forests, and extreme gradient boosting). The DBNs generated by RAUS achieved 73-83% area under the receiver operating characteristic curve (AUCROC) within 24-hours before AKI; and 71-79% AUCROC within 48-hours before AKI of any stage in a 7-day observation window. Insights from this automated framework can help efficiently implement and interpret DBNs for clinical decision support. The source code for RAUS is available in GitHub at https://github.com/dgrdn08/RAUS .

YongKyung Oh, Henry W. Zheng, Jeffrey Feng et al.

Machine Learning (ML) models trained on complex health surveys such as the National Health and Nutrition Examination Survey (NHANES) often ignore primary sampling units, stratification variables, and sampling weights. This practice violates the independence assumptions of standard evaluation methods. As a result, estimates become biased, uncertainty is underestimated, and fairness assessments fail to reflect population-level disparities. We propose Survey-aware Machine Learning (SaML), a nine-step guideline that incorporates survey design metadata across the ML lifecycle. Through a scoping review of 16 methodological papers, we summarize existing work on weighted model training, design-based cross-validation, and survey-adjusted performance evaluation. We also identify gaps in hyperparameter tuning and deployment. We provide task-specific guidance that clarifies which steps are required for different analytical objectives. SaML provides a checklist for valid population inference from survey data.

Simha Sankar Baradwaj, Destiny Gilliland, Jack Rincon et al.

Foundational Models (FMs) are gaining increasing attention in the biomedical AI ecosystem due to their ability to represent and contextualize multimodal biomedical data. These capabilities make FMs a valuable tool for a variety of tasks, including biomedical reasoning, hypothesis generation, and interpreting complex imaging data. In this review paper, we address the unique challenges associated with establishing an ethical and trustworthy biomedical AI ecosystem, with a particular focus on the development of FMs and their downstream applications. We explore strategies that can be implemented throughout the biomedical AI pipeline to effectively tackle these challenges, ensuring that these FMs are translated responsibly into clinical and translational settings. Additionally, we emphasize the importance of key stewardship and co-design principles that not only ensure robust regulation but also guarantee that the interests of all stakeholders, especially those involved in or affected by these clinical and translational applications are adequately represented. We aim to empower the biomedical AI community to harness these models responsibly and effectively. As we navigate this exciting frontier, our collective commitment to ethical stewardship, co-design, and responsible translation will be instrumental in ensuring that the evolution of FMs truly enhances patient care and medical decision making, ultimately leading to a more equitable and trustworthy biomedical AI ecosystem.

YongKyung Oh, Seungsu Kam, Jonghun Lee et al.

Time series modeling and analysis have become critical in various domains. Conventional methods such as RNNs and Transformers, while effective for discrete-time and regularly sampled data, face significant challenges in capturing the continuous dynamics and irregular sampling patterns inherent in real-world scenarios. Neural Differential Equations (NDEs) represent a paradigm shift by combining the flexibility of neural networks with the mathematical rigor of differential equations. This paper presents a comprehensive review of NDE-based methods for time series analysis, including neural ordinary differential equations, neural controlled differential equations, and neural stochastic differential equations. We provide a detailed discussion of their mathematical formulations, numerical methods, and applications, highlighting their ability to model continuous-time dynamics. Furthermore, we address key challenges and future research directions. This survey serves as a foundation for researchers and practitioners seeking to leverage NDEs for advanced time series analysis.

John Rincon, Alexander R. Pelletier, Destiny Gilliland et al.

Objective: As AI becomes increasingly central to healthcare, there is a pressing need for bioinformatics and biomedical training systems that are personalized and adaptable. Materials and Methods: The NIH Bridge2AI Training, Recruitment, and Mentoring (TRM) Working Group developed a cross-disciplinary curriculum grounded in collaborative innovation, ethical data stewardship, and professional development within an adapted Learning Health System (LHS) framework. Results: The curriculum integrates foundational AI modules, real-world projects, and a structured mentee-mentor network spanning Bridge2AI Grand Challenges and the Bridge Center. Guided by six learner personas, the program tailors educational pathways to individual needs while supporting scalability. Discussion: Iterative refinement driven by continuous feedback ensures that content remains responsive to learner progress and emerging trends. Conclusion: With over 30 scholars and 100 mentors engaged across North America, the TRM model demonstrates how adaptive, persona-informed training can build interdisciplinary competencies and foster an integrative, ethically grounded AI education in biomedical contexts.

YongKyung Oh, Dong-Young Lim, Sungil Kim et al.

Handling missing data in time series classification remains a significant challenge in various domains. Traditional methods often rely on imputation, which may introduce bias or fail to capture the underlying temporal dynamics. In this paper, we propose TANDEM (Temporal Attention-guided Neural Differential Equations for Missingness), an attention-guided neural differential equation framework that effectively classifies time series data with missing values. Our approach integrates raw observation, interpolated control path, and continuous latent dynamics through a novel attention mechanism, allowing the model to focus on the most informative aspects of the data. We evaluate TANDEM on 30 benchmark datasets and a real-world medical dataset, demonstrating its superiority over existing state-of-the-art methods. Our framework not only improves classification accuracy but also provides insights into the handling of missing data, making it a valuable tool in practice.

Irsyad Adam, Steven Swee, Erika Yilin et al.

In this work, we study the problem pertaining to personalized classification of subclinical atherosclerosis by developing a hierarchical graph neural network framework to leverage two characteristic modalities of a patient: clinical features within the context of the cohort, and molecular data unique to individual patients. Current graph-based methods for disease classification detect patient-specific molecular fingerprints, but lack consistency and comprehension regarding cohort-wide features, which are an essential requirement for understanding pathogenic phenotypes across diverse atherosclerotic trajectories. Furthermore, understanding patient subtypes often considers clinical feature similarity in isolation, without integration of shared pathogenic interdependencies among patients. To address these challenges, we introduce ATHENA: Atherosclerosis Through Hierarchical Explainable Neural Network Analysis, which constructs a novel hierarchical network representation through integrated modality learning; subsequently, it optimizes learned patient-specific molecular fingerprints that reflect individual omics data, enforcing consistency with cohort-wide patterns. With a primary clinical dataset of 391 patients, we demonstrate that this heterogeneous alignment of clinical features with molecular interaction patterns has significantly boosted subclinical atherosclerosis classification performance across various baselines by up to 13% in area under the receiver operating curve (AUC) and 20% in F1 score. Taken together, ATHENA enables mechanistically-informed patient subtype discovery through explainable AI (XAI)-driven subnetwork clustering; this novel integration framework strengthens personalized intervention strategies, thereby improving the prediction of atherosclerotic disease progression and management of their clinical actionable outcomes.

Erika Yilin Zheng, Yu Yan, Baradwaj Simha Sankar et al.

Existing machine learning methods for molecular (e.g., gene) embeddings are restricted to specific tasks or data modalities, limiting their effectiveness within narrow domains. As a result, they fail to capture the full breadth of gene functions and interactions across diverse biological contexts. In this study, we have systematically evaluated knowledge representations of biomolecules across multiple dimensions representing a task-agnostic manner spanning three major data sources, including omics experimental data, literature-derived text data, and knowledge graph-based representations. To distinguish between meaningful biological signals from chance correlations, we devised an adjusted variant of Singular Vector Canonical Correlation Analysis (SVCCA) that quantifies signal redundancy and complementarity across different data modalities and sources. These analyses reveal that existing embeddings capture largely non-overlapping molecular signals, highlighting the value of embedding integration. Building on this insight, we propose Platform for Representation and Integration of multimodal Molecular Embeddings (PRISME), a machine learning based workflow using an autoencoder to integrate these heterogeneous embeddings into a unified multimodal representation. We validated this approach across various benchmark tasks, where PRISME demonstrated consistent performance, and outperformed individual embedding methods in missing value imputations. This new framework supports comprehensive modeling of biomolecules, advancing the development of robust, broadly applicable multimodal embeddings optimized for downstream biomedical machine learning applications.

YongKyung Oh, Alex Bui

Adapting machine learning models to medical time series across different domains remains a challenge due to complex temporal dependencies and dynamic distribution shifts. Current approaches often focus on isolated feature representations, limiting their ability to fully capture the intricate temporal dynamics necessary for robust domain adaptation. In this work, we propose a novel framework leveraging multi-view contrastive learning to integrate temporal patterns, derivative-based dynamics, and frequency-domain features. Our method employs independent encoders and a hierarchical fusion mechanism to learn feature-invariant representations that are transferable across domains while preserving temporal coherence. Extensive experiments on diverse medical datasets, including electroencephalogram (EEG), electrocardiogram (ECG), and electromyography (EMG) demonstrate that our approach significantly outperforms state-of-the-art methods in transfer learning tasks. By advancing the robustness and generalizability of machine learning models, our framework offers a practical pathway for deploying reliable AI systems in diverse healthcare settings.

David Gordon, Panayiotis Petousis, Susanne B. Nicholas et al.

Diagnostic reasoning entails a physician's local (mental) model based on an assumed or known shared perspective (global model) to explain patient observations with evidence assigned towards a clinical assessment. But in several (complex) medical situations, multiple experts work together as a team to optimize health evaluation and decision-making by leveraging different perspectives. Such consensus-driven reasoning reflects individual knowledge contributing toward a broader perspective on the patient. In this light, we introduce STRUCture-following for Multiagent Systems (STRUC-MAS), a framework automating the learning of these global models and their incorporation as prior beliefs for agents in multiagent systems (MAS) to follow. We demonstrate proof of concept with a prosocial MAS application for predicting acute kidney injuries (AKIs). In this case, we found that incorporating a global structure enabled multiple agents to achieve better performance (average precision, AP) in predicting AKI 48 hours before onset (structure-following-fine-tuned, SF-FT, AP=0.195; SF-FT-retrieval-augmented generation, SF-FT-RAG, AP=0.194) vs. baseline (non-structure-following-FT, NSF-FT, AP=0.141; NSF-FT-RAG, AP=0.180) for balanced precision-weighted-recall-weighted voting. Markedly, SF-FT agents with higher recall scores reported lower confidence levels in the initial round on true positive and false negative cases. But after explicit interactions, their confidence in their decisions increased (suggesting reinforced belief). In contrast, the SF-FT agent with the lowest recall decreased its confidence in true positive and false negative cases (suggesting a new belief). This approach suggests that learning and leveraging global structures in MAS is necessary prior to achieving competitive classification and diagnostic reasoning performance.

Panayiotis Petousis, David Gordon, Susanne B. Nicholas et al.

Randomized controlled trials (RCTs) are the standard for evaluating the effectiveness of clinical interventions. To address the limitations of RCTs on real-world populations, we developed a methodology that uses a large observational electronic health record (EHR) dataset. Principles of regression discontinuity (rd) were used to derive randomized data subsets to test expert-driven interventions using dynamic Bayesian Networks (DBNs) do-operations. This combined method was applied to a chronic kidney disease (CKD) cohort of more than two million individuals and used to understand the associational and causal relationships of CKD variables with respect to a surrogate outcome of >=40% decline in estimated glomerular filtration rate (eGFR). The associational and causal analyses depicted similar findings across DBNs from two independent healthcare systems. The associational analysis showed that the most influential variables were eGFR, urine albumin-to-creatinine ratio, and pulse pressure, whereas the causal analysis showed eGFR as the most influential variable, followed by modifiable factors such as medications that may impact kidney function over time. This methodology demonstrates how real-world EHR data can be used to provide population-level insights to inform improved healthcare delivery.

Bilwaj Gaonkar, Joel Beckett, Mark Attiah et al.

Translation of fully automated deep learning based medical image segmentation technologies to clinical workflows face two main algorithmic challenges. The first, is the collection and archival of large quantities of manually annotated ground truth data for both training and validation. The second is the relative inability of the majority of deep learning based segmentation techniques to alert physicians to a likely segmentation failure. Here we propose a novel algorithm, named `Eigenrank' which addresses both of these challenges. Eigenrank can select for manual labeling, a subset of medical images from a large database, such that a U-Net trained on this subset is superior to one trained on a randomly selected subset of the same size. Eigenrank can also be used to pick out, cases in a large database, where deep learning segmentation will fail. We present our algorithm, followed by results and a discussion of how Eigenrank exploits the Von Neumann information to perform both data subset selection and failure prediction for medical image segmentation using deep learning.

Bilwaj Gaonkar, Matthew Edwards, Alex Bui et al.

Yes, it can. Data augmentation is perhaps the oldest preprocessing step in computer vision literature. Almost every computer vision model trained on imaging data uses some form of augmentation. In this paper, we use the inter-vertebral disk segmentation task alongside a deep residual U-Net as the learning model, to explore the effectiveness of augmentation. In the extreme, we observed that a model trained on patches extracted from just one scan, with each patch augmented 50 times; achieved a Dice score of 0.73 in a validation set of 40 cases. Qualitative evaluation indicated a clinically usable segmentation algorithm, which appropriately segments regions of interest, alongside limited false positive specks. When the initial patches are extracted from nine scans the average Dice coefficient jumps to 0.86 and most of the false positives disappear. While this still falls short of state-of-the-art deep learning based segmentation of discs reported in literature, qualitative examination reveals that it does yield segmentation, which can be amended by expert clinicians with minimal effort to generate additional data for training improved deep models. Extreme augmentation of training data, should thus be construed as a strategy for training deep learning based algorithms, when very little manually annotated data is available to work with. Models trained with extreme augmentation can then be used to accelerate the generation of manually labelled data. Hence, we show that extreme augmentation can be a valuable tool in addressing scaling up small imaging data sets to address medical image segmentation tasks.

Shiwen Shen, Simon X. Han, Denise R. Aberle et al.

While deep learning methods are increasingly being applied to tasks such as computer-aided diagnosis, these models are difficult to interpret, do not incorporate prior domain knowledge, and are often considered as a "black-box." The lack of model interpretability hinders them from being fully understood by target users such as radiologists. In this paper, we present a novel interpretable deep hierarchical semantic convolutional neural network (HSCNN) to predict whether a given pulmonary nodule observed on a computed tomography (CT) scan is malignant. Our network provides two levels of output: 1) low-level radiologist semantic features, and 2) a high-level malignancy prediction score. The low-level semantic outputs quantify the diagnostic features used by radiologists and serve to explain how the model interprets the images in an expert-driven manner. The information from these low-level tasks, along with the representations learned by the convolutional layers, are then combined and used to infer the high-level task of predicting nodule malignancy. This unified architecture is trained by optimizing a global loss function including both low- and high-level tasks, thereby learning all the parameters within a joint framework. Our experimental results using the Lung Image Database Consortium (LIDC) show that the proposed method not only produces interpretable lung cancer predictions but also achieves significantly better results compared to common 3D CNN approaches.