Genre
PRSformer: Disease Prediction from Million-Scale Individual Genotypes
Predicting disease risk from DNA presents an unprecedented emerging challenge as biobanks approach population scale sizes (N > 106 individuals) with ultra-highdimensional features (L > 105 genotypes). Current methods, often linear and reliant on summary statistics, fail to capture complex genetic interactions and discard valuable individual-level information. We introduce PRSformer, a scalable deep learning architecture designed for end-to-end, multitask disease prediction directly from million-scale individual genotypes. PRSformer employs neighborhood attention, achieving linear O(L) complexity per layer, making Transformers tractable for genome-scale inputs. Crucially, PRSformer utilizes a stacking of these efficient attention layers, progressively increasing the effective receptive field to model local dependencies (e.g., within linkage disequilibrium blocks) before integrating information across wider genomic regions. This design, tailored for genomics, allows PRSformer to learn complex, potentially non-linear and long-range interactions directly from raw genotypes. We demonstrate PRSformer's effectiveness using a unique large private cohort (N 5M) for predicting 18 autoimmune and inflammatory conditions using L 140k variants. PRSformer significantly outperforms highly optimized linear models trained on the same individual-level data and state-of-the-art summary-statistic-based methods (LDPred2) derived from the same cohort, quantifying the benefits of non-linear modeling and multitask learning at scale. Furthermore, experiments reveal that the advantage of non-linearity emerges primarily at large sample sizes (N > 1M), and that a multi-ancestry trained model improves generalization, establishing PRSformer as a new framework for deep learning in population-scale genomics.
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Series Section Electron Microscopy (ssEM) has emerged as a pivotal technology for deciphering nanoscale biological architectures. Three-dimensional (3D) registration is a critical step in ssEM, tasked with rectifying axial misalignments and nonlinear distortions introduced during serial sectioning. The core scientific challenge lies in achieving distortion mitigation without erasing the natural morphological deformations of biological tissues, thereby enabling faithful reconstruction of 3D ultrastructural organization. In this study, we present a paradigm-shifting optimization framework that rethinks 3D registration through the lens of manifold trajectory optimization. We propose the first continuous trajectory dynamics formulation for 3D registration and introduce a novel optimization strategy. Specifically, we introduce a dual optimization objective that inherently balances global trajectory smoothness with local structural preservation, while developing a solver that combines Gauss-Seidel iteration with Neural ODEs to systematically integrate biophysical priors with data-driven deformation compensation. Extensive experiments on multiple datasets spanning diverse tissue types demonstrate our method's superior performance in structural restoration accuracy and cross-tissue robustness.
AStatistical Theory of Contrastive Learning via Approximate Sufficient Statistics
Contrastive learning--a modern approach to extract useful representations from unlabeled data by training models to distinguish similar samples from dissimilar ones--has driven significant progress in foundation models. In this work, we develop a new theoretical framework for analyzing data augmentation-based contrastive learning, with a focus on SimCLR as a representative example. Our approach is based on the concept of approximate sufficient statistics, which we extend beyond its original definition in Oko et al. [28] for contrastive languageimage pretraining (CLIP) using KL-divergence. We generalize it to equivalent forms and general f-divergences, and show that minimizing SimCLR and other contrastive losses yields encoders that are approximately sufficient. Furthermore, we demonstrate that these near-sufficient encoders can be effectively adapted to downstream regression and classification tasks, with performance depending on their sufficiency and the error induced by data augmentation in contrastive learning. Concrete examples in linear regression and topic classification are provided to illustrate the broad applicability of our results.
PolyJuice Makes It Real: Black-Box, Universal Red Teaming for Synthetic Image Detectors
Synthetic image detectors (SIDs) are a key defense against the risks posed by the growing realism of images from text-to-image (T2I) models. Red teaming improves SID's effectiveness by identifying and exploiting their failure modes via misclassified synthetic images. However, existing red-teaming solutions (i) require white-box access to SIDs, which is infeasible for proprietary state-of-the-art detectors, and (ii) generate image-specific attacks through expensive online optimization. To address these limitations, we propose PolyJuice, the first black-box, imageagnostic red-teaming method for SIDs, based on an observed distribution shift in the T2I latent space between samples correctly and incorrectly classified by the SID. PolyJuice generates attacks by (i) identifying the direction of this shift through a lightweight offline process that only requires black-box access to the SID, and (ii) exploiting this direction by universally steering all generated images towards the SID's failure modes. PolyJuice-steered T2I models are significantly more effective at deceiving SIDs (up to 84%) compared to their unsteered counterparts. We also show that the steering directions can be estimated efficiently at lower resolutions and transferred to higher resolutions using simple interpolation, reducing computational overhead. Finally, tuning SID models on PolyJuice-augmented datasets notably enhances the performance of the detectors (up to 30%).
Universal Visuo-Tactile Video Understanding for Embodied Interaction
Tactile perception is essential for embodied agents to understand physical attributes of objects that cannot be determined through visual inspection alone. While existing approaches have made progress in visual and language modalities for physical understanding, they fail to effectively incorporate tactile information that provides crucial haptic feedback for real-world interaction.
Minimax-Optimal Univariate Function Selection in Sparse Additive Models: Rates, Adaptation, and the Estimation-Selection Gap
The sparse additive model (SpAM) offers a trade-off between interpretability and flexibility, and hence is a powerful model for high-dimensional research. This paper focuses on the variable selection, i.e., the univariate function selection problem in SpAM. We establish the minimax separation rates from both the perspectives of sparse multiple testing (FDR + FNR control) and support recovery (wrong recovery probability control). We further study how adaptation to unknown smoothness affects the minimax separation rate, and propose an adaptive selection procedure. Finally, we discuss the difference between estimation and selection in SpAM: Procedures achieving optimal function estimation may fail to achieve optimal univariate function selection.
Reconciling Geospatial Prediction and Retrieval via Sparse Representations
Urban computing harnesses big data to decode complex urban dynamics and revolutionize location-based services. Traditional approaches have treated geospatial prediction tasks (e.g., estimating socio-economic indicators) and retrieval tasks (e.g., querying geographic objects) as isolated challenges, necessitating separate models with distinct training objectives. This fragmentation imposes significant computational burdens and limits cross-task synergy, despite advances in representation learning and multi-task foundation models.