Eran Segal

David Krongauz, Arad Zulti, Eran Segal et al.

Automatic scientific discovery has long been a goal of computational scholars - a machine that can discover nature's secrets on its own, moving computational systems beyond data-fitting tools toward the generation and refinement of mechanistic models of the universe. Recent advances in symbolic regression (SR) and large-language-model (LLM)-based agents suggest that such systems can recover equations from data, incorporate domain priors, and automate parts of the research workflow. However, most existing approaches either focus on narrow equation-discovery benchmarks or broad end-to-end automation pipelines, while biological systems remain comparatively underexplored. Here, we introduce the MEDA system, an LLM- and SR-powered agentic framework for discovering ordinary-differential-equation (ODE) models of biological and biologically inspired dynamical systems. MEDA retrieves background knowledge, defines admissible variables, generates mechanistic constraints, proposes candidate ODEs, and fits and evaluates them. We evaluate it across canonical model retrieval, reasoning-based extrapolation to unseen variants, and open-ended discovery, with and without experimental data. Across these settings, MEDA recovered the correct state variables, achieved strong structural recovery in retrieval and extrapolation tasks, and produced biologically plausible discovery-oriented models. Ablation and robustness analyses show that knowledge-guided formalization and mechanistic constraints are load-bearing components, whereas numerical fitting alone can preserve trajectory-compatible but biologically incorrect equations.

Li Zhang, Basu Jindal, Ahmed Alaa et al.

Semantic segmentation of medical images is pivotal in applications like disease diagnosis and treatment planning. While deep learning has excelled in automating this task, a major hurdle is the need for numerous annotated segmentation masks, which are resource-intensive to produce due to the required expertise and time. This scenario often leads to ultra low-data regimes, where annotated images are extremely limited, posing significant challenges for the generalization of conventional deep learning methods on test images. To address this, we introduce a generative deep learning framework, which uniquely generates high-quality paired segmentation masks and medical images, serving as auxiliary data for training robust models in data-scarce environments. Unlike traditional generative models that treat data generation and segmentation model training as separate processes, our method employs multi-level optimization for end-to-end data generation. This approach allows segmentation performance to directly influence the data generation process, ensuring that the generated data is specifically tailored to enhance the performance of the segmentation model. Our method demonstrated strong generalization performance across 9 diverse medical image segmentation tasks and on 16 datasets, in ultra-low data regimes, spanning various diseases, organs, and imaging modalities. When applied to various segmentation models, it achieved performance improvements of 10-20\% (absolute), in both same-domain and out-of-domain scenarios. Notably, it requires 8 to 20 times less training data than existing methods to achieve comparable results. This advancement significantly improves the feasibility and cost-effectiveness of applying deep learning in medical imaging, particularly in scenarios with limited data availability.

Guy Lutsker, Gal Sapir, Smadar Shilo et al.

Recent advances in SSL enabled novel medical AI models, known as foundation models, offer great potential for better characterizing health from diverse biomedical data. CGM provides rich, temporal data on glycemic patterns, but its full potential for predicting broader health outcomes remains underutilized. Here, we present GluFormer, a generative foundation model for CGM data that learns nuanced glycemic patterns and translates them into predictive representations of metabolic health. Trained on over 10 million CGM measurements from 10,812 adults, primarily without diabetes, GluFormer uses autoregressive token prediction to capture longitudinal glucose dynamics. We show that GluFormer generalizes to 19 external cohorts (n=6,044) spanning different ethnicities and ages, 5 countries, 8 CGM devices, and diverse pathophysiological states. GluFormers representations exceed the performance of current CGM metrics, such as the Glucose Management Indicator (GMI), for forecasting clinical measures. In a longitudinal study of 580 adults with CGM data and 12-year follow-up, GluFormer identifies individuals at elevated risk of developing diabetes more effectively than blood HbA1C%, capturing 66% of all new-onset diabetes diagnoses in the top quartile versus 7% in the bottom quartile. Similarly, 69% of cardiovascular-death events occurred in the top quartile with none in the bottom quartile, demonstrating powerful risk stratification beyond traditional glycemic metrics. We also show that CGM representations from pre-intervention periods in Randomized Clinical Trials outperform other methods in predicting primary and secondary outcomes. When integrating dietary data into GluFormer, we show that the multi-modal version of the model can accurately generate CGM data based on dietary intake data, simulate outcomes of dietary interventions, and predict individual responses to specific foods.

Alon Diament, Maria Gorodetski, Adam Jankelow et al.

This study introduces a novel, rich dataset obtained from home sleep apnea tests using the FDA-approved WatchPAT-300 device, collected from 7,077 participants over 21,412 nights. The dataset comprises three levels of sleep data: raw multi-channel time-series from sensors, annotated sleep events, and computed summary statistics, which include 447 features related to sleep architecture, sleep apnea, and heart rate variability (HRV). We present reference values for Apnea/Hypopnea Index (AHI), sleep efficiency, Wake After Sleep Onset (WASO), and HRV sample entropy, stratified by age and sex. Moreover, we demonstrate that the dataset improves the predictive capability for various health related traits, including body composition, bone density, blood sugar levels and cardiovascular health. These results illustrate the dataset's potential to advance sleep research, personalized healthcare, and machine learning applications in biomedicine.

Ira Shavitt, Eran Segal

Despite their impressive performance, Deep Neural Networks (DNNs) typically underperform Gradient Boosting Trees (GBTs) on many tabular-dataset learning tasks. We propose that applying a different regularization coefficient to each weight might boost the performance of DNNs by allowing them to make more use of the more relevant inputs. However, this will lead to an intractable number of hyperparameters. Here, we introduce Regularization Learning Networks (RLNs), which overcome this challenge by introducing an efficient hyperparameter tuning scheme which minimizes a new Counterfactual Loss. Our results show that RLNs significantly improve DNNs on tabular datasets, and achieve comparable results to GBTs, with the best performance achieved with an ensemble that combines GBTs and RLNs. RLNs produce extremely sparse networks, eliminating up to 99.8% of the network edges and 82% of the input features, thus providing more interpretable models and reveal the importance that the network assigns to different inputs. RLNs could efficiently learn a single network in datasets that comprise both tabular and unstructured data, such as in the setting of medical imaging accompanied by electronic health records. An open source implementation of RLN can be found at https://github.com/irashavitt/regularization_learning_networks.

Yuewen Sun, Lingjing Kong, Guangyi Chen et al.

Prevalent in biomedical applications (e.g., human phenotype research), multimodal datasets can provide valuable insights into the underlying physiological mechanisms. However, current machine learning (ML) models designed to analyze these datasets often lack interpretability and identifiability guarantees, which are essential for biomedical research. Recent advances in causal representation learning have shown promise in identifying interpretable latent causal variables with formal theoretical guarantees. Unfortunately, most current work on multimodal distributions either relies on restrictive parametric assumptions or yields only coarse identification results, limiting their applicability to biomedical research that favors a detailed understanding of the mechanisms. In this work, we aim to develop flexible identification conditions for multimodal data and principled methods to facilitate the understanding of biomedical datasets. Theoretically, we consider a nonparametric latent distribution (c.f., parametric assumptions in previous work) that allows for causal relationships across potentially different modalities. We establish identifiability guarantees for each latent component, extending the subspace identification results from previous work. Our key theoretical contribution is the structural sparsity of causal connections between modalities, which, as we will discuss, is natural for a large collection of biomedical systems. Empirically, we present a practical framework to instantiate our theoretical insights. We demonstrate the effectiveness of our approach through extensive experiments on both numerical and synthetic datasets. Results on a real-world human phenotype dataset are consistent with established biomedical research, validating our theoretical and methodological framework.

Guy Lutsker, Hagai Rossman, Nastya Godiva et al.

Substantial advances in multi-modal Artificial Intelligence (AI) facilitate the combination of diverse medical modalities to achieve holistic health assessments. We present COMPRER , a novel multi-modal, multi-objective pretraining framework which enhances medical-image representation, diagnostic inferences, and prognosis of diseases. COMPRER employs a multi-objective training framework, where each objective introduces distinct knowledge to the model. This includes a multimodal loss that consolidates information across different imaging modalities; A temporal loss that imparts the ability to discern patterns over time; Medical-measure prediction adds appropriate medical insights; Lastly, reconstruction loss ensures the integrity of image structure within the latent space. Despite the concern that multiple objectives could weaken task performance, our findings show that this combination actually boosts outcomes on certain tasks. Here, we apply this framework to both fundus images and carotid ultrasound, and validate our downstream tasks capabilities by predicting both current and future cardiovascular conditions. COMPRER achieved higher Area Under the Curve (AUC) scores in evaluating medical conditions compared to existing models on held-out data. On the Out-of-distribution (OOD) UK-Biobank dataset COMPRER maintains favorable performance over well-established models with more parameters, even though these models were trained on $75\times$ more data than COMPRER. In addition, to better assess our model's performance in contrastive learning, we introduce a novel evaluation metric, providing deeper understanding of the effectiveness of the latent space pairing.

Yingxu Wang, Kunyu Zhang, Jiaxin Huang et al.

Multimodal molecular representation learning, which jointly models molecular graphs and their textual descriptions, enhances predictive accuracy and interpretability by enabling more robust and reliable predictions of drug toxicity, bioactivity, and physicochemical properties through the integration of structural and semantic information. However, existing multimodal methods suffer from two key limitations: (1) they typically perform cross-modal interaction only at the final encoder layer, thus overlooking hierarchical semantic dependencies; (2) they lack a unified prototype space for robust alignment between modalities. To address these limitations, we propose ProtoMol, a prototype-guided multimodal framework that enables fine-grained integration and consistent semantic alignment between molecular graphs and textual descriptions. ProtoMol incorporates dual-branch hierarchical encoders, utilizing Graph Neural Networks to process structured molecular graphs and Transformers to encode unstructured texts, resulting in comprehensive layer-wise representations. Then, ProtoMol introduces a layer-wise bidirectional cross-modal attention mechanism that progressively aligns semantic features across layers. Furthermore, a shared prototype space with learnable, class-specific anchors is constructed to guide both modalities toward coherent and discriminative representations. Extensive experiments on multiple benchmark datasets demonstrate that ProtoMol consistently outperforms state-of-the-art baselines across a variety of molecular property prediction tasks.

Huifa Li, Feilong Tang, Haochen Xue et al.

Aging is a highly complex and heterogeneous process that progresses at different rates across individuals, making biological age (BA) a more accurate indicator of physiological decline than chronological age. While previous studies have built aging clocks using single-omics data, they often fail to capture the full molecular complexity of human aging. In this work, we leveraged the Human Phenotype Project, a large-scale cohort of 10,000 adults aged 40-70 years, with extensive longitudinal profiling that includes clinical, behavioral, environmental, and multi-omics datasets spanning transcriptomics, lipidomics, metabolomics, and the microbiome. By employing advanced machine learning frameworks capable of modeling nonlinear biological dynamics, we developed and rigorously validated a multi-omics aging clock that robustly predicts diverse health outcomes and future disease risk. Unsupervised clustering of the integrated molecular profiles from multi-omics uncovered distinct biological subtypes of aging, revealing striking heterogeneity in aging trajectories and pinpointing pathway-specific alterations associated with different aging patterns. These findings demonstrate the power of multi-omics integration to decode the molecular landscape of aging and lay the groundwork for personalized healthspan monitoring and precision strategies to prevent age-related diseases.

Hido Pinto, Eran Segal

Machine learning has been successfully used in critical domains, such as medicine. However, extracting meaningful insights from biomedical data is often constrained by the lack of their available disease labels. In this research, we demonstrate how machine learning can be leveraged to enhance explainability and uncover biologically meaningful associations, even when predictive improvements in disease modeling are limited. We train LightGBM models from scratch on our dataset (10K) to impute metabolomics features and apply them to the UK Biobank (UKBB) for downstream analysis. The imputed metabolomics features are then used in survival analysis to assess their impact on disease-related risk factors. As a result, our approach successfully identified biologically relevant connections that were not previously known to the predictive models. Additionally, we applied a genome-wide association study (GWAS) on key metabolomics features, revealing a link between vascular dementia and smoking. Although being a well-established epidemiological relationship, this link was not embedded in the model's training data, which validated the method's ability to extract meaningful signals. Furthermore, by integrating survival models as inputs in the 10K data, we uncovered associations between metabolic substances and obesity, demonstrating the ability to infer disease risk for future patients without requiring direct outcome labels. These findings highlight the potential of leveraging external bio-banks to extract valuable biomedical insights, even in data-limited scenarios. Our results demonstrate that machine learning models trained on smaller datasets can still be used to uncover real biological associations when carefully integrated with survival analysis and genetic studies.

Uri Lerner, Eran Segal, Daphne Koller

Many real life domains contain a mixture of discrete and continuous variables and can be modeled as hybrid Bayesian Networks. Animportant subclass of hybrid BNs are conditional linear Gaussian (CLG) networks, where the conditional distribution of the continuous variables given an assignment to the discrete variables is a multivariate Gaussian. Lauritzen's extension to the clique tree algorithm can be used for exact inference in CLG networks. However, many domains also include discrete variables that depend on continuous ones, and CLG networks do not allow such dependencies to berepresented. No exact inference algorithm has been proposed for these enhanced CLG networks. In this paper, we generalize Lauritzen's algorithm, providing the first "exact" inference algorithm for augmented CLG networks - networks where continuous nodes are conditional linear Gaussians but that also allow discrete children ofcontinuous parents. Our algorithm is exact in the sense that it computes the exact distributions over the discrete nodes, and the exact first and second moments of the continuous ones, up to the accuracy obtained by numerical integration used within thealgorithm. When the discrete children are modeled with softmax CPDs (as is the case in many real world domains) the approximation of the continuous distributions using the first two moments is particularly accurate. Our algorithm is simple to implement and often comparable in its complexity to Lauritzen's algorithm. We show empirically that it achieves substantially higher accuracy than previous approximate algorithms.

Eran Segal, Dana Pe'er, Aviv Regev et al.

Methods for learning Bayesian network structure can discover dependency structure between observed variables, and have been shown to be useful in many applications. However, in domains that involve a large number of variables, the space of possible network structures is enormous, making it difficult, for both computational and statistical reasons, to identify a good model. In this paper, we consider a solution to this problem, suitable for domains where many variables have similar behavior. Our method is based on a new class of models, which we call module networks. A module network explicitly represents the notion of a module - a set of variables that have the same parents in the network and share the same conditional probability distribution. We define the semantics of module networks, and describe an algorithm that learns a module network from data. The algorithm learns both the partitioning of the variables into modules and the dependency structure between the variables. We evaluate our algorithm on synthetic data, and on real data in the domains of gene expression and the stock market. Our results show that module networks generalize better than Bayesian networks, and that the learned module network structure reveals regularities that are obscured in learned Bayesian networks.