#01Nov 10, 2026
cs.AI
Contrastive Discovery: Open-Ended Scientific Discovery over Competing Explanations
Ziang Liu, James J. Kim, Yijia Dai and 1 more
LLM agents are increasingly used for open-ended, data-driven scientific discovery, yet most of them evaluate hypotheses pointwise, testing an empirical claim $h$ only against its complement $\neg h$. When evidence rejects $h$, the agent learns that one explanation is unlikely but not which alternative the evidence supports. To recover that alternative, we introduce Contrastive Discovery, which replaces the single hypothesis with a contrast set, a scientific question paired with mutually exclusive and collectively exhaustive competing explanations. Each experiment is scored by how its evidence redistributes belief across the set, and the question is resolved when belief concentrates on one explanation. Because contrast sets change only the unit an agent proposes and scores, an existing agent can use them to re-evaluate evidence it has already collected or to guide its search. Across six domains, $89\%$ of the pointwise candidates with the largest belief shifts are rejections. On the same evidence, contrast sets resolve $73\%$ of these candidates to a specific alternative. When contrast sets guide search, the agent resolves $67\%$ more questions than pointwise surprisal under the same experiment budget. In a blinded study, $38$ human experts chose the same explanation on $78\%$ of resolved questions and on $82\%$ of questions where the pointwise agent rejected its hypothesis and stopped. Together, these results support explicit competing explanations as a way for discovery agents to resolve more scientific questions from the same evidence and validation budget.
#02Nov 10, 2026
cs.LG
Emergent Biological Capabilities in a Foundation Model for Molecular Interactions
Adi Mashiach
Foundation models trained on large unlabeled corpora develop emergent capabilities, tasks that go beyond the training objective. We extend this paradigm to multimodal biology with Bonbon, a foundation model for molecular interactions trained on approximately 3.2 trillion tokens of paired protein-ligand sequences. From a single representation space, Bonbon exhibits three zero-shot emergent capabilities at hierarchical levels of resolution: functional (mechanism of action), residue (binding site localization, including orthosteric/allosteric discrimination), and bond (covalent versus non-covalent engagement). All three capabilities generalize to out-of-distribution complexes. Bonbon was trained on protein-ligand sequences alone, without any task-specific supervision and without structural coordinates. We conducted controlled scaling experiments across six model scales from 42M to 1.6B parameters; every capability evaluated shows a sharp jump at the largest scale on continuous metrics, even as pretraining loss decreases smoothly. This demonstrates that loss-based scaling laws alone are insufficient to predict when zero-shot emergent capabilities become available. The capabilities reported here emerge after training at a 1:2,000 parameter-to-token ratio to accommodate the sparsity of paired biological interaction data. The same frozen representations achieve state-of-the-art binding and affinity prediction at five orders of magnitude greater speed than co-folding methods. In prospective wet-lab validation across nine disease targets spanning seven protein families, Bonbon achieves a 61.5% dose-response hit rate on de novo compounds, yielding structurally novel molecules not previously reported to inhibit these proteins, including for out-of-distribution targets.
#03Nov 10, 2026
cs.CV
RS-JEPA: Remote Sensing Joint-Embedding Predictive Architecture with Scan-Path Views for Cross-Sensor Image Retrieval
Tanishq Rachamalla, Srishti Kaushik, Muhammad Attique Khan and 2 more
Cross-sensor remote sensing image retrieval aims to find scenes with the same content across heterogeneous sensors, such as SAR and optical or panchromatic (PAN) and multispectral (MS) imagery, without manual labels. Existing self-supervised methods either reconstruct sensor-specific pixel detail, align each image only with its co-registered twin, or rely on large transformers with 118-173M parameters (and up to 398M). We introduce RS-JEPA, a compact joint-embedding predictive framework built on a Vision Mamba encoder shared by both sensors. Since a state-space encoder reads an image as an ordered sequence of patches, we propose scan-path views, which treat two reading orders of the same image as two views with identical pixels and predict the hidden patches in one order from the visible patches in the other.To keep this prediction challenging, we propose Adversarial View Coupling (AVC), which learns the hardest split of the visible patches, and a neighbourhood consensus loss that aligns the scene similarities of both sensors. Extensive experiments on SAR-optical (BEN-14K, CBRSIR-VS) and PAN-MS (DSRSID) benchmarks demonstrate that RS-JEPA achieves the highest F1@5 among twelve re-implemented methods (72.92, 80.35 and 94.43) with a retrieval network of only 3.88M parameters (14.57M in training, 8-16times fewer than prior JEPA retrievers). Like prior methods, RS-JEPA trains on co-registered pairs. Our results highlight reading order as a source of self-supervised views. code: https://github.com/Tanishq251/RSJEPA.
#04Nov 10, 2026
cs.CV
Toward Foundation Detection Models via Example-Based Grounding in EM-DETR
Sheethal Bhat, Bogdan Georgescu, Awais Mansoor and 3 more
DeepLearning (DL)-based Computer-Aided Diagnostic (CAD) systems have shown great promise in supporting clinicians, but their performance heavily depends on the availability of large, well-annotated datasets. In medical lesion detection, the scarcity of comprehensive, stan dardized annotations and the heterogeneity of existing datasets limit the development of robust foundation models. In this work, we introduce a novel approach to building a multi-domain foundation model for le sion detection by integrating diverse medical image datasets annotated for both anatomical structures and abnormalities. We first propose a student-teacher training strategy to effectively combine datasets with heterogeneous label spaces, mitigating catastrophic forgetting, and im proving feature learning. In addition, building on our previously pro posed example-based EM-DETR framework, we adapt it to jointly learn from multiple domain-specific datasets, enabling fine-grained, example driven detection across modalities. Our model achieves state-of-the-art (SOTA) results, with image-level AUC scores exceeding previous SOTA by 1% point on four key findings in CXRs. We achieve a leading mAP50 in CXRs and mammography, surpassing EM-DETR trained on a single dataset by 2-3% points. This approach paves the way for scalable foundation models in medical imaging that leverage heterogeneous data while maintaining robust and generalizable performance.
#05Nov 10, 2026
stat.ML
A Theory of Cross-Validation Variance
Nathaniel S. O'Connell, Jaime L. Speiser
Cross-validation estimates predictive performance by repeatedly splitting the data into training and validation sets, fitting the model on the first and evaluating it on the second. Every observation influences the estimate in two roles, through its own evaluation when it is held out and through the models it helps fit when it trains. The random splits determine its weight in each role. From this representation, we prove an exact finite-sample identity for the variance of the cross-validated estimate. For a given splitting scheme with a common training set size, the variance is a function of these weights, with constants of the model, the metric, and the population. It covers metrics averaged over observations, such as mean squared error, and over case--control pairs, such as the AUC. The identity shows which schemes to use. The variance decomposes into sampling variance, which depends only on the training size, and variance due to the random fold splitting, which arises when the weights change from one draw of the splits to the next. K-fold cross-validation, whose weights are equal across observations by design, is therefore variance optimal at first order; Monte Carlo and bootstrap cross-validation are not. The first-order variance of K-fold does not depend on K, and under reasonable conditions on the model leave-one-out has the smallest variance of any K-fold scheme. For the AUC the same holds for leave-pair-out, which evaluates every case--control pair. Finally, we show the cross-validated estimate is asymptotically normal with the identity's full variance. Together, these results provide a general theoretical foundation for inference on cross-validated performance and establish principles for selecting variance-optimal cross-validation designs.