arXiv subjects

Julien Bodelet

Publications and source records attributed to Julien Bodelet.

3 recordsLinked to original sources

arXiv2025

Physics-Informed Neural Koopman Machine for Interpretable Longitudinal Personalized Alzheimer's Disease Forecasting

Early forecasting of individual cognitive decline in Alzheimer's disease (AD) is central to disease evaluation and management. Despite advances, it is as of yet challenging for existing methodological frameworks to integrate multimodal data for longitudinal personalized forecasting while maintaining interpretability. To address this gap, we present the Neural Koopman Machine (NKM), a new machine learning architecture inspired by dynamical systems and attention mechanisms, designed to forecast multiple cognitive scores simultaneously using multimodal genetic, neuroimaging, proteomic, and demographic data. NKM integrates analytical ($\alpha$) and biological ($\beta$) knowledge to guide feature grouping and control the hierarchical attention mechanisms to extract relevant patterns. By implementing Fusion Group-Aware Hierarchical Attention within the Koopman operator framework, NKM transforms complex nonlinear trajectories into interpretable linear representations. To demonstrate NKM's efficacy, we applied it to study the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Our results suggest that NKM consistently outperforms both traditional machine learning methods and deep learning models in forecasting trajectories of cognitive decline. Specifically, NKM (1) forecasts changes of multiple cognitive scores simultaneously, (2) quantifies differential biomarker contributions to predicting distinctive cognitive scores, and (3) identifies brain regions most predictive of cognitive deterioration. Together, NKM advances personalized, interpretable forecasting of future cognitive decline in AD using past multimodal data through an explainable, explicit system and reveals potential multimodal biological underpinnings of AD progression.

cs.LG↗

arXiv2025

OPTIMUS: Predicting Multivariate Outcomes in Alzheimer's Disease Using Multi-modal Data amidst Missing Values

Alzheimer's disease, a neurodegenerative disorder, is associated with neural, genetic, and proteomic factors while affecting multiple cognitive and behavioral faculties. Traditional AD prediction largely focuses on univariate disease outcomes, such as disease stages and severity. Multimodal data encode broader disease information than a single modality and may, therefore, improve disease prediction; but they often contain missing values. Recent "deeper" machine learning approaches show promise in improving prediction accuracy, yet the biological relevance of these models needs to be further charted. Integrating missing data analysis, predictive modeling, multimodal data analysis, and explainable AI, we propose OPTIMUS, a predictive, modular, and explainable machine learning framework, to unveil the many-to-many predictive pathways between multimodal input data and multivariate disease outcomes amidst missing values. OPTIMUS first applies modality-specific imputation to uncover data from each modality while optimizing overall prediction accuracy. It then maps multimodal biomarkers to multivariate outcomes using machine-learning and extracts biomarkers respectively predictive of each outcome. Finally, OPTIMUS incorporates XAI to explain the identified multimodal biomarkers. Using data from 346 cognitively normal subjects, 608 persons with mild cognitive impairment, and 251 AD patients, OPTIMUS identifies neural and transcriptomic signatures that jointly but differentially predict multivariate outcomes related to executive function, language, memory, and visuospatial function. Our work demonstrates the potential of building a predictive and biologically explainable machine-learning framework to uncover multimodal biomarkers that capture disease profiles across varying cognitive landscapes. The results improve our understanding of the complex many-to-many pathways in AD.

cs.LG↗

arXiv2020

Statistical Quantile Learning for Large, Nonlinear, and Additive Latent Variable Models

The studies of large-scale, high-dimensional data in fields such as genomics and neuroscience have injected new insights into science. Yet, despite advances, they are confronting several challenges, often simultaneously: lack of interpretability, nonlinearity, slow computation, inconsistency and uncertain convergence, and small sample sizes compared to high feature dimensions. Here, we propose a relatively simple, scalable, and consistent nonlinear dimension reduction method that can potentially address these issues in unsupervised settings. We call this method Statistical Quantile Learning (SQL) because, methodologically, it leverages on a quantile approximation of the latent variables together with standard nonparametric techniques (sieve or penalyzed methods). We show that estimating the model simplifies into a convex assignment matching problem; we derive its asymptotic properties; we show that the model is identifiable under few conditions. Compared to its linear competitors, SQL explains more variance, yields better separation and explanation, and delivers more accurate outcome prediction. Compared to its nonlinear competitors, SQL shows considerable advantage in interpretability, ease of use and computations in large-dimensional settings. Finally, we apply SQL to high-dimensional gene expression data (consisting of 20,263 genes from 801 subjects), where the proposed method identified latent factors predictive of five cancer types. The SQL package is available at https://github.com/jbodelet/SQL.

stat.ME↗