Classifying antimicrobial peptides(AMPs) from the vast array of peptides mined from metagenomic sequencing data is a significant approach to addressing the issue of antibiotic resistance. However, current AMP classification methods, primarily relying on sequence-based data, neglect the spatial structure of peptides, thereby limiting the accurate classification of AMPs. Additionally, the number of known AMPs is significantly lower than that of non-AMPs, leading to imbalanced datasets that reduce predictive accuracy for AMPs. To alleviate these two limitations, we first employ Omegafold to predict the three-dimensional spatial structures of AMPs and non-AMPs, constructing peptide graphs based on the amino acids' C$_\alpha$ positions. Building upon this, we propose a novel classification model named Spatial GNN-based AMP Classifier (SGAC). Our SGAC model employs a graph encoder based on Graph Neural Networks (GNNs) to process peptide graphs, generating high-dimensional representations that capture essential features from the three-dimensional spatial structure of amino acids. Then, to address the inherent imbalanced datasets, SGAC first incorporates Weight-enhanced Contrastive Learning, which clusters similar peptides while ensuring separation between dissimilar ones, using weighted contributions to emphasize AMP-specific features. Furthermore, SGAC employs Weight-enhanced Pseudo-label Distillation to dynamically generate high-confidence pseudo labels for ambiguous peptides, further refining predictions and promoting balanced learning between AMPs and non-AMPs. Experiments on publicly available AMP and non-AMP datasets demonstrate that SGAC significantly outperforms traditional sequence-based methods and achieves state-of-the-art performance among graph-based models, validating its effectiveness in AMP classification.

Biology lies at the core of vital fields such as medicine, pharmacy, public health, longevity, agriculture and food security, environmental protection, and clean energy. The mechanisms underlying living and physical systems have always fascinated us. With Newton's laws, we can predict the orbits of celestial bodies; the periodic table allows us to anticipate the properties of chemical compounds; and we can even simulate weather and environmental systems. However, despite our extensive knowledge of atomic, molecular, chemical, and physical laws, and the computational power of modern computers, we still cannot simulate biological systems accurately. Whether we aim to pinpoint genetic markers of diseases for diagnosis, design drugs to heal damaged cells or deter pathogens, or develop vaccines to combat pandemics, such advancements in medicine consistently require a profound understanding of the underlying biology at all levels, along with the ability to predict, simulate, and program biological activities comprehensively. Manipulating biology in the physical world is extremely complex, expensive, and risky, and should be preceded by extensive computer-aided digital design, simulation, and validation as in other industrial fields such as civil, nuclear, and semiconductor engineering. We propose a vision in which such capabilities can be realized using generative AI. Generative AI and large pretrained models across text, images, speech, and video have become key pillars for advancing artificial general intelligence (AGI), driving significant improvements in a wide range of downstream tasks, including language and image comprehension, translation, knowledge extraction, reasoning, and cross-modal generation. These models are often known as "foundation

Prevalent in biological applications (e.g., human phenotype measurements), multimodal datasets can provide valuable insights into the underlying biological mechanisms. However, current machine learning models designed to analyze such datasets still lack interpretability and theoretical guarantees, which are essential to biological applications. Recent advances in causal representation learning have shown promise in uncovering the interpretable latent causal variables with formal theoretical certificates. Unfortunately, existing works for multimodal distributions either rely on restrictive parametric assumptions or provide rather coarse identification results, limiting their applicability to biological research which 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 biological datasets. Theoretically, we consider a flexible nonparametric latent distribution (c.f., parametric assumptions in prior work) permitting causal relationships across potentially different modalities. We establish identifiability guarantees for each latent component, extending the subspace identification results from prior work. Our key theoretical ingredient is the structural sparsity of the causal connections among distinct modalities, which, as we will discuss, is natural for a large collection of biological systems. Empirically, we propose 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 medical research, validating our theoretical and methodological framework.

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.

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.

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.

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.

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 that 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.

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.

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.