Julien Bodelet

Georgi Hrusanov, Oliver Y. Chén, Julien S. Bodelet

Deep Generative models (DGMs) play two key roles in modern machine learning: (i) producing new information (e.g., image synthesis) and (ii) reducing dimensionality. However, traditional architectures often rely on auxiliary networks such as encoders in Variational Autoencoders (VAEs) or discriminators in Generative Adversarial Networks (GANs), which introduce training instability, computational overhead, and risks like mode collapse. We present NeuroSQL, a new generative paradigm that eliminates the need for auxiliary networks by learning low-dimensional latent representations implicitly. NeuroSQL leverages an asymptotic approximation that expresses the latent variables as the solution to an optimal transportation problem. Specifically, NeuroSQL learns the latent variables by solving a linear assignment problem and then passes the latent information to a standalone generator. We benchmark its performance against GANs, VAEs, and a budget-matched diffusion baseline on four datasets: handwritten digits (MNIST), faces (CelebA), animal faces (AFHQ), and brain images (OASIS). Compared to VAEs, GANs, and diffusion models: (1) in terms of image quality, NeuroSQL achieves overall lower mean pixel distance between synthetic and authentic images and stronger perceptual/structural fidelity; (2) computationally, NeuroSQL requires the least training time; and (3) practically, NeuroSQL provides an effective solution for generating synthetic data with limited training samples. By embracing quantile assignment rather than an encoder, NeuroSQL provides a fast, stable, and robust way to generate synthetic data with minimal information loss.

Christelle Schneuwly Diaz, Duy-Thanh Vu, Julien Bodelet et al.

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.