medical data teams

Abstract: We study density ratio estimation and importance-weighted regression under target shift with continuous outputs. Under target shift, the conditional distribution of the inputs given the outputs remains invariant across the training and test distributions, while the output marginal distribution may change. Although this problem has been extensively studied for discrete outputs, the continuous setting is substantially less understood: the importance weights are determined by an unknown density ratio function, for which existing estimation methods lack explicit finite-sample convergence rates. We propose a spectral regularization method in a reproducing kernel Hilbert space (RKHS) for estimating the continuous density ratio from labeled training samples and unlabeled test inputs. Under a source condition with regularity parameter $ι>0$, we establish high-probability finite-sample guarantees and show that the estimator achieves the capacity-independent minimax-optimal RKHS-norm rate $O(n_η^{-ι/(2ι+2)})$. We then incorporate the estimated density ratio into importance-weighted regression and characterize the propagation of density-ratio estimation error to the final predictor. When sufficiently many samples are available for density ratio estimation, the resulting regression estimator attains the minimax-optimal rates of standard kernel regression. These results establish a finite-sample theory for continuous density ratio estimation and importance-weighted learning under target shift.

Abstract: Formal explainability of classifying neural networks (NNs) is an active area of research, providing explanations with provable guarantees of the classification within continuous regions of the input feature space. However, the existing techniques are either limited to individual input features without guarantees on their relations or the provided solutions fail to scale to deep architectures. This paper addresses these issues by introducing a flexible symbolic framework for an efficient, guided computation of explanations of the NN behavior, parametrized by the activations of internal neurons, and using logical engines such as SMT solvers. Unlike prior methods that rely on specialized NN verifiers, our method yields explanations that are not restricted in shape. Our algorithm is implementable on top of a general-purpose logical solver, isolating the NN-specific encoding from the algorithmic framework. We experimented with a wide range of benchmarks from the domains of image recognition and medicine, illustrating the advantages of the new method, particularly in computational efficiency. Notably, our approach enables logical explanation of deep networks not amenable to prior logic-based methods.

Abstract: Aging clocks quantify biological aging and help characterize individual health status. What protein interactions are important for accurate aging clocks, and are they zeroth-order or higher-order? Addressing these questions requires learning from large molecular datasets distributed across medical centers, where privacy constraints prevent centralized data sharing. Federated learning offers a natural solution but faces four challenges in this setting: limited local sample sizes, sparse and directional inter-center trust, the need to retain discriminative age prediction while supporting interpretation, and model drift and forgetting under heterogeneous cross-center data. We propose TNFL, a trust-network-based federated learning framework that progressively propagates models along directed pairwise trust relations without centralized aggregation. TNFL combines an age-aware mixture-of-experts model with generative replay to preserve previously learned information and reduce forgetting and drift. Experiments across multiple molecular datasets show that TNFL enables effective aging-clock prediction with limited local data, provides interpretable age-dependent prediction patterns, and maintains stable performance across interaction orders. To investigate the biological questions, we analyze TNFL-identified pairwise protein interactions and their higher-order organization through functional and network analyses. The identified interactions repeatedly form coordinated higher-order subnetworks spanning multiple aging-related biological systems, with several proteins recurring across subnetworks. These findings suggest that TNFL captures molecular relationships beyond isolated pairwise associations and reveals coherent higher-order biological organization associated with aging.