#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.CL
Mechanistic Interpretability Needs a Logic of Inference
Zhimin Hu, Chen Jiang, Hanbo Xie and 2 more
Neural networks are increasingly studied not merely as predictive systems, but as complex systems whose internal computations are themselves objects of scientific inquiry. Recent progress in mechanistic interpretability (MI) has made it possible to identify neurons, features, circuits, population structures, and dynamical patterns associated with model behavior. As these tools improve, attention is shifting from what can be observed inside a model to how those observations support mechanistic explanations. We examine the parallel efforts of neuroscience and MI to address this question and identify recurring inferential bottlenecks when inferring mechanisms from complex neural systems. We propose five principles and organize them into a recursive logic for a more rigorous procedure of mechanistic inference. These principles provide a framework that supports scientific discovery in two senses: it helps turn local interpretability findings into cumulative knowledge of mechanisms within models, and it makes those mechanisms sufficiently precise to generate testable hypotheses about domains beyond the models. Evidence beyond MI is ultimately required to establish what model mechanisms reveal about the world.
#03Nov 10, 2026
cs.CV
BoviShift: A Six-Year Multi-Attribute Audit of Visual Cattle Phenotyping Across Animals and Time
Mobasshir Bhuiya Shagor, Nilambar Halder Tonmoy, Md Saef Ullah Miah
Computer vision offers a scalable, non-contact means of estimating livestock traits, but correlated images and video frames make reliable evaluation difficult. Image-random splitting can place views of the same animal in both training and test sets, while deployment further requires transfer to animals captured in future years. We introduce BoviShift, a corpus reconstructed from six consecutive annual cohorts of an operational cattle marketplace collected from 2021 to 2026. It contains 2{,}657 cattle, 10{,}610 still images, and 2{,}566 walk-around videos across nine recorded breed categories. We evaluate three splitting strategies through four configurations: image-random and pooled cattle-disjoint splits over the same development cohorts, followed by separate future-2025 and locked future-2026 evaluations. Using a fixed ResNet-50 multi-task baseline, we assess weight, age, height, breed, and coat color. Differences between image-random and cattle-disjoint splitting are task-dependent rather than a universal leakage penalty. Future-cohort behavior is also attribute- and cohort-specific: breed declines relative to pooled evaluation; mean weight and age performance fails to beat constant baselines in 2025; height remains above baseline; and color transfers well to 2025 but degrades in 2026. Multi-task training improves all five point estimates in a single-seed ablation, still-view aggregation helps selectively, and zero-shot video-frame aggregation exposes a still-to-video domain gap. To our knowledge, BoviShift is the longest-spanning cattle-vision resource combining consecutive annual cohorts with physical and visual attributes.
#04Nov 10, 2026
cs.IR
FERN: Cross-Benchmark Table Retrieval for Text-to-SQL with Frozen Retrievers and Learned Ranking
Arjun Rao, Nishant Gopinath
Text-to-SQL systems over large pooled catalogs must first retrieve the tables a question needs. We compare against the published table recall of RASL, which uses Claude 3.5 models to extract keywords and select tables, on pooled BIRD, Spider, and Fiben catalogs. FERN (Feature-Engineered Ranking with No generative LLM) instead fuses three frozen retrievers into 100 candidates, describes each with up to 120 features, and reorders them with LightGBM rankers fitted once on BIRD's training questions. On Spider, where it was not fitted, its candidate pool alone reaches RASL's published recall at fifteen tables (98.0), and the ranker raises the share of questions with every gold table in the top five (complete@5) from 83.9% to 95.6%. At five tables, FERN's recall is within one point of RASL's on Spider (96.7 vs 97.0) and on BIRD with its evidence hints (96.6 vs 97.5), and 8.2 points below on BIRD without them (89.3). On 121 real BEAVER questions, without BEAVER fitting, its recall at fifteen (82.1) falls between two BEAVER-trained retrievers (80.8, 84.5), but its complete@15 is below both (49.6 vs 54.5 and 62.0). On Fiben, it falls far short at fifteen tables (54.2 vs 69.2, different question sets), although its recall at fifty is numerically close to RASL's question-only retrieval result (80.7 vs 79.4). On BIRD dev with evidence, non-retrieval features raise complete@5 by 7.7 points over retrieval signals alone. On BIRD dev, median latency is 208 ms per question on one A100, without hosted model calls.
#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.