Probabilities of causation play a crucial role in modern decision-making. This paper addresses the challenge of predicting probabilities of causation for subpopulations with insufficient data using machine learning models. Tian and Pearl first defined and derived tight bounds for three fundamental probabilities of causation: the probability of necessity and sufficiency (PNS), the probability of sufficiency (PS), and the probability of necessity (PN). However, estimating these probabilities requires both experimental and observational distributions specific to each subpopulation, which are often unavailable or impractical to obtain with limited population-level data. We assume that the probabilities of causation for each subpopulation are determined by its characteristics. To estimate these probabilities for subpopulations with insufficient data, we propose using machine learning models that draw insights from subpopulations with sufficient data. Our evaluation of multiple machine learning models indicates that, given sufficient population-level data and an appropriate choice of machine learning model and activation function, PNS can be effectively predicted. Through simulation studies, we show that our multilayer perceptron (MLP) model with the Mish activation function achieves a mean absolute error (MAE) of approximately 0.02 in predicting PNS for 32,768 subpopulations using data from around 2,000 subpopulations.

Taste peptides have emerged as promising natural flavoring agents attributed to their unique organoleptic properties, high safety profile, and potential health benefits. However, the de novo identification of taste peptides derived from animal, plant, or microbial sources remains a time-consuming and resource-intensive process, significantly impeding their widespread application in the food industry. Here, we present TastePepAI, a comprehensive artificial intelligence framework for customized taste peptide design and safety assessment. As the key element of this framework, a loss-supervised adaptive variational autoencoder (LA-VAE) is implemented to efficiently optimizes the latent representation of sequences during training and facilitates the generation of target peptides with desired taste profiles. Notably, our model incorporates a novel taste-avoidance mechanism, allowing for selective flavor exclusion. Subsequently, our in-house developed toxicity prediction algorithm (SpepToxPred) is integrated in the framework to undergo rigorous safety evaluation of generated peptides. Using this integrated platform, we successfully identified 73 peptides exhibiting sweet, salty, and umami, significantly expanding the current repertoire of taste peptides. This work demonstrates the potential of TastePepAI in accelerating taste peptide discovery for food applications and provides a versatile framework adaptable to broader peptide engineering challenges.

We consider the problem of matrix completion with graphs as side information depicting the interrelations between variables. The key challenge lies in leveraging the similarity structure of the graph to enhance matrix recovery. Existing approaches, primarily based on graph Laplacian regularization, suffer from several limitations: (1) they focus only on the similarity between neighboring variables, while overlooking long-range correlations; (2) they are highly sensitive to false edges in the graphs and (3) they lack theoretical guarantees regarding statistical and computational complexities. To address these issues, we propose in this paper a novel graph regularized matrix completion algorithm called GSGD, based on preconditioned projected gradient descent approach. We demonstrate that GSGD effectively captures the higher-order correlation information behind the graphs, and achieves superior robustness and stability against the false edges. Theoretically, we prove that GSGD achieves linear convergence to the global optimum with near-optimal sample complexity, providing the first theoretical guarantees for both recovery accuracy and efficacy in the perspective of nonconvex optimization. Our numerical experiments on both synthetic and real-world data further validate that GSGD achieves superior recovery accuracy and scalability compared with several popular alternatives.

Many hardware proposals have aimed to accelerate inference in AI workloads. Less attention has been paid to hardware acceleration of training, despite the enormous societal impact of rapid training of AI models. Physics-based computers, such as thermodynamic computers, offer an efficient means to solve key primitives in AI training algorithms. Optimizers that normally would be computationally out-of-reach (e.g., due to expensive matrix inversions) on digital hardware could be unlocked with physics-based hardware. In this work, we propose a scalable algorithm for employing thermodynamic computers to accelerate a popular second-order optimizer called Kronecker-factored approximate curvature (K-FAC). Our asymptotic complexity analysis predicts increasing advantage with our algorithm as $n$, the number of neurons per layer, increases. Numerical experiments show that even under significant quantization noise, the benefits of second-order optimization can be preserved. Finally, we predict substantial speedups for large-scale vision and graph problems based on realistic hardware characteristics.

Binary classification is a task that involves the classification of data into one of two distinct classes. It is widely utilized in various fields. However, conventional classifiers tend to make overconfident predictions for data that belong to overlapping regions of the two class distributions or for data outside the distributions (out-of-distribution data). Therefore, conventional classifiers should not be applied in high-risk fields where classification results can have significant consequences. In order to address this issue, it is necessary to quantify uncertainty and adopt decision-making approaches that take it into account. Many methods have been proposed for this purpose; however, implementing these methods often requires performing resampling, improving the structure or performance of models, and optimizing the thresholds of classifiers. We propose a new decision-making approach using two types of hypothesis testing. This method is capable of detecting ambiguous data that belong to the overlapping regions of two class distributions, as well as out-of-distribution data that are not included in the training data distribution. In addition, we quantify uncertainty using the empirical distribution of feature values derived from the training data obtained through the trained model. The classification threshold is determined by the $\alpha$-quantile and ($1-\alpha$)-quantile, where the significance level $\alpha$ is set according to each specific situation.

The adoption of EHRs has expanded opportunities to leverage data-driven algorithms in clinical care and research. A major bottleneck in effectively conducting multi-institutional EHR studies is the data heterogeneity across systems with numerous codes that either do not exist or represent different clinical concepts across institutions. The need for data privacy further limits the feasibility of including multi-institutional patient-level data required to study similarities and differences across patient subgroups. To address these challenges, we developed the GAME algorithm. Tested and validated across 7 institutions and 2 languages, GAME integrates data in several levels: (1) at the institutional level with knowledge graphs to establish relationships between codes and existing knowledge sources, providing the medical context for standard codes and their relationship to each other; (2) between institutions, leveraging language models to determine the relationships between institution-specific codes with established standard codes; and (3) quantifying the strength of the relationships between codes using a graph attention network. Jointly trained embeddings are created using transfer and federated learning to preserve data privacy. In this study, we demonstrate the applicability of GAME in selecting relevant features as inputs for AI-driven algorithms in a range of conditions, e.g., heart failure, rheumatoid arthritis. We then highlight the application of GAME harmonized multi-institutional EHR data in a study of Alzheimer's disease outcomes and suicide risk among patients with mental health disorders, without sharing patient-level data outside individual institutions.

Differentiating signals from the background in micrographs is a critical initial step for cryogenic electron microscopy (cryo-EM), yet it remains laborious due to low signal-to-noise ratio (SNR), the presence of contaminants and densely packed particles of varying sizes. Although image segmentation has recently been introduced to distinguish particles at the pixel level, the low SNR complicates the automated generation of accurate annotations for training supervised models. Moreover, platforms for systematically comparing different design choices in pipeline construction are lacking. Thus, a modular framework is essential to understand the advantages and limitations of this approach and drive further development. To address these challenges, we present a pipeline that automatically generates high-quality segmentation maps from cryo-EM data to serve as ground truth labels. Our modular framework enables the selection of various segmentation models and loss functions. We also integrate Conditional Random Fields (CRFs) with different solvers and feature sets to refine coarse predictions, thereby producing fine-grained segmentation. This flexibility facilitates optimal configurations tailored to cryo-EM datasets. When trained on a limited set of micrographs, our approach achieves over 90% accuracy, recall, precision, Intersection over Union (IoU), and F1-score on synthetic data. Furthermore, to demonstrate our framework's efficacy in downstream analyses, we show that the particles extracted by our pipeline produce 3D density maps with higher resolution than those generated by existing particle pickers on real experimental datasets, while achieving performance comparable to that of manually curated datasets from experts.

Time is implicitly embedded in classification process: classifiers are usually built on existing data while to be applied on future data whose distributions (e.g., label and token) may change. However, existing state-of-the-art classification models merely consider the temporal variations and primarily focus on English corpora, which leaves temporal studies less explored, let alone under multilingual settings. In this study, we fill the gap by treating time as domains (e.g., 2024 vs. 2025), examining temporal effects, and developing a domain adaptation framework to generalize classifiers over time on multiple languages. Our framework proposes Mixture of Temporal Experts (MoTE) to leverage both semantic and data distributional shifts to learn and adapt temporal trends into classification models. Our analysis shows classification performance varies over time across different languages, and we experimentally demonstrate that MoTE can enhance classifier generalizability over temporal data shifts. Our study provides analytic insights and addresses the need for time-aware models that perform robustly in multilingual scenarios.

We introduce k-LLMmeans, a novel modification of the k-means clustering algorithm that utilizes LLMs to generate textual summaries as cluster centroids, thereby capturing contextual and semantic nuances often lost when relying on purely numerical means of document embeddings. This modification preserves the properties of k-means while offering greater interpretability: the cluster centroid is represented by an LLM-generated summary, whose embedding guides cluster assignments. We also propose a mini-batch variant, enabling efficient online clustering for streaming text data and providing real-time interpretability of evolving cluster centroids. Through extensive simulations, we show that our methods outperform vanilla k-means on multiple metrics while incurring only modest LLM usage that does not scale with dataset size. Finally, We present a case study showcasing the interpretability of evolving cluster centroids in sequential text streams. As part of our evaluation, we compile a new dataset from StackExchange, offering a benchmark for text-stream clustering.

The growing availability of longitudinal Magnetic Resonance Imaging (MRI) datasets has facilitated Artificial Intelligence (AI)-driven modeling of disease progression, making it possible to predict future medical scans for individual patients. However, despite significant advancements in AI, current methods continue to face challenges including achieving patient-specific individualization, ensuring spatiotemporal consistency, efficiently utilizing longitudinal data, and managing the substantial memory demands of 3D scans. To address these challenges, we propose Brain Latent Progression (BrLP), a novel spatiotemporal model designed to predict individual-level disease progression in 3D brain MRIs. The key contributions in BrLP are fourfold: (i) it operates in a small latent space, mitigating the computational challenges posed by high-dimensional imaging data; (ii) it explicitly integrates subject metadata to enhance the individualization of predictions; (iii) it incorporates prior knowledge of disease dynamics through an auxiliary model, facilitating the integration of longitudinal data; and (iv) it introduces the Latent Average Stabilization (LAS) algorithm, which (a) enforces spatiotemporal consistency in the predicted progression at inference time and (b) allows us to derive a measure of the uncertainty for the prediction. We train and evaluate BrLP on 11,730 T1-weighted (T1w) brain MRIs from 2,805 subjects and validate its generalizability on an external test set comprising 2,257 MRIs from 962 subjects. Our experiments compare BrLP-generated MRI scans with real follow-up MRIs, demonstrating state-of-the-art accuracy compared to existing methods. The code is publicly available at: https://github.com/LemuelPuglisi/BrLP.