#01Nov 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.
#02Nov 10, 2026
cs.SD
Exploring Post-Hoc Disentanglement of Audio Foundation Models for Music Similarity
Lucas de Souza Brandão, Gabriel da Costa Merlin, Diego Furtado Silva
Audio foundation models like CLAP, MuQ, and MERT excel at capturing general musical similarity. On the other hand, their entangled latent spaces limit interpretability and fine-grained attribute control. Conditional Similarity Networks (CSN) address this by pairing a backbone representation model with learned masks that gate the embedding space into attribute-specific subspaces. However, existing methods train the backbone from scratch, rather than leveraging pretrained foundation models. We instead present a systematic study of post-hoc disentanglement, adapting CSN to gate frozen pretrained embeddings. We evaluate adding trainable parameters to adapt the embedding under different masking and pooling regimes across two datasets. Our findings show that minimal adaptation capacity is sufficient for post-hoc gating to improve both attribute-specific disentanglement and overall retrieval performance, while pooling, masking, and depth choices yield limited additional gains.
#03Nov 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.
#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
cs.LG
DnNP: Denoising Input Uncertainty in Neural Processes
Fatemeh Tohidian, Chengzhi Shi, Soomi Lee and 4 more
Neural Processes (NPs) are flexible meta-learning models capable of uncertainty quantification across diverse applications. However, the standard NP framework assumes access to noise-free inputs. This is unrealistic in many practical settings, where sensor noise or measurement errors are unavoidable. This discrepancy between model assumptions and real-world data can significantly degrade prediction quality and uncertainty estimates. We introduce Denoising Neural Processes (DnNPs), a principled extension of the NP framework that explicitly models input uncertainty. We train DnNPs via variational inference. DnNPs jointly learn to denoise corrupted inputs and perform meta-learning, making them robust to noisy training data. We demonstrate DnNPs' effectiveness on both synthetic and real-world datasets, showing consistent improvements in prediction and uncertainty quantification compared to standard NPs. On PM2.5 spatial interpolation from real-world air quality sensors, DnNP reduces RMSE by up to 30% and NLL by up to 73% relative to standard NPs. We also provide theoretical grounding: we show that the Bayes-optimal predictor under noisy inputs belongs to the DnNP model class, and that plug-in models with fixed observation variance incur an irreducible KL divergence gap that DnNP provably avoids.