Abstract:In multi-modal biomedical research, integrating high-dimensional genomic data with clinical baselines is essential for precision medicine. However, standard deep neural network approaches often entangle these modalities, obscuring the specific predictive impact of genetic features and leading to possibly suboptimal predictive performance. Motivated by the landmark METABRIC cohort primary breast tumors study, we propose the Stein-Encoder, a white-box supervised framework designed to isolate the genetic signal driving clinical outcomes conditional on nuisance covariates. By leveraging Stein's method and residualization techniques, our approach constructs an interpretable single index that summarizes relevant biological heterogeneity while flexibly incorporating clinical factors and can be used to improve downstream prediction. We establish theoretical guarantees for identification, consistency and efficiency improvement. Applied to the METABRIC cohort, the Stein-Encoder outperforms unsupervised benchmarks in predictive accuracy. Crucially, it achieves structural disentanglement by revealing response-specific biological mechanisms: we find that tumor size is driven primarily by mitotic networks, whereas prognostic indices rely on a distinct proliferation-versus-immune axis. This work contributes a unified, computationally efficient framework that bridges statistical rigor with the representational power of neural networks, enabling interpretable, task-specific and efficient compression of multi-modal health data for a wide range of precision medicine applications, beyond biomarker discovery.
Abstract:Ordinary differential equations (ODEs) provide a powerful framework for modeling dynamic systems arising in a wide range of scientific domains. However, most existing ODE methods focus on a single system, and do not adequately address the problem of learning shared patterns from multiple heterogeneous dynamic systems. In this article, we propose a novel distributionally robust learning approach for modeling heterogeneous ODE systems. Specifically, we construct a robust dynamic system by maximizing a worst-case reward over an uncertainty class formed by convex combinations of the derivatives of trajectories. We show the resulting estimator admits an explicit weighted average representation, where the weights are obtained from a quadratic optimization that balances information across multiple data sources. We further develop a bi-level stabilization procedure to address potential instability in estimation. We establish rigorous theoretical guarantees for the proposed method, including consistency of the stabilized weights, error bound for robust trajectory estimation, and asymptotical validity of pointwise confidence interval. We demonstrate that the proposed method considerably improves the generalization performance compared to the alternative solutions through both extensive simulations and the analysis of an intracranial electroencephalogram data.
Abstract:Brain encoding and decoding aims to understand the relationship between external stimuli and brain activities, and is a fundamental problem in neuroscience. In this article, we study latent embedding alignment for brain encoding and decoding, with a focus on improving sample efficiency under limited fMRI-stimulus paired data and substantial subject heterogeneity. We propose a lightweight alignment framework equipped with two statistical learning components: inverse semi-supervised learning that leverages abundant unpaired stimulus embeddings through inverse mapping and residual debiasing, and meta transfer learning that borrows strength from pretrained models across subjects via sparse aggregation and residual correction. Both methods operate exclusively at the alignment stage while keeping encoders and decoders frozen, allowing for efficient computation, modular deployment, and rigorous theoretical analysis. We establish finite-sample generalization bounds and safety guarantees, and demonstrate competitive empirical performance on the large-scale fMRI-image reconstruction benchmark data.