#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
When Does the Real Wiring Win? Testing connectome structure-function claims against unmeasured physiology
Yeyuan Liu
Connectome-constrained models are often used to argue that a measured wiring diagram outperforms shuffled or rewired wiring, and hence that structure shapes function. Such comparisons can confound wiring with how the models are tuned: a connectome fixes who connects to whom, not the excitability, gains or plasticity rates the model also needs, and modellers often tune these until the real-wiring model works. We separate three estimands: physiology tuned on the real wiring and transferred to nulls (P1), each wiring tuned on its own (P2), and P2 restricted to physiology consistent with independent data (P3). The biases involved are known in machine learning (under-tuned baselines, inherited weights, winner's curse); we measure what they do to biological conclusions, using synthetic ground truth, placebo nulls and three Drosophila circuit models. Some claims survive every protocol we test: segregated reward and punishment dopamine improves learning, and head-direction topography is required for a persistent bump. Others do not. In the mushroom body, the real Kenyon-cell output wiring beats a cross-subtype identity shuffle by 0.09 under P1 and P2 but loses to it by 0.09 under P3 (95% CIs exclude zero; held-out runs confirm). The verdict is set by the share of alpha'beta' cells among active Kenyon cells, which P1 selects low; at the share implied by imaging (about 44%) the real-wiring model fails to learn, exposing a model inadequacy rather than a deficit of the fly's wiring. In flyvis, P1 penalises a mirrored connectome, which has a constructed solution within 0.07 (median) of the real error, more than a spatially shuffled one in 50 of 50 members; the ranking survives ten-fold longer retraining but depends on the checkpoint at fifty-fold. A credible structural claim needs matched optimisation, data-constrained physiology and a model that still works there.
#03Nov 10, 2026
cs.LG
TorchCurves: Differentiable Parametric Curves
Alex Shtoff
We present TorchCurves, a PyTorch library that treats vector-valued parametric curves as learnable primitives. Its central operation maps batches of scalar inputs to points on curves represented in B-spline or Legendre polynomial bases, with differentiation through both inputs and coefficients. Curve coefficients can be optimized jointly with the surrounding model or produced by another network. The library provides trainable modules, reusable basis modules, and a functional interface, supporting applications ranging from continuous feature embeddings to Kolmogorov-Arnold networks and functional regression. Its implementation combines classical evaluation algorithms with vectorized PyTorch operations, emphasizing readability and maintainability without custom hardware kernels. Timing experiments compare curve evaluation against NumPy and SciPy and KAN training against EfficientKAN across a range of problem sizes. The results illustrate where this generality remains computationally practical and where overhead is substantial. Library is available on GitHub at https://github.com/alexshtf/torchcurves.
#04Nov 10, 2026
cs.LG
Pyrite: Building and Benchmarking Protein-Ligand Pose Ranking Agents
Megha Srivastava, Michael H. Lim, Allison M. Keys and 2 more
Predicting how a ligand binds to its target is central to small-molecule drug discovery. Modern cofolding models can generate diverse candidate poses, but reliably ranking these candidates remains challenging. We introduce Pyrite, a pairwise pose-ranking benchmark comprising 1,500 pose pairs across diverse protein-ligand complexes. Expert chemists equipped with 3D visualization tools and physics-based scores perform near chance, highlighting the difficulty of interpreting available chemical signals. To investigate automated ranking, we introduce PyriteRep, a structured representation of molecular geometry, protein-ligand interactions, and physicochemical scores, and develop two LLM-based agents: PyriteReasoner, which directly compares poses through text-based reasoning, and PyriteFeaturizer, which generates executable code to construct features for logistic regression, optionally incorporating features derived from LLM subcalls. These agents achieve up to 67% and 74% accuracy, respectively, exceeding observed expert performance. LLM-guided feature discovery generally outperforms direct reasoning, while Group Relative Policy Optimization (GRPO) improves open-weight models, enabling them to match or surpass closed-source frontier models in our evaluations. These results establish Pyrite as a challenging test of pose-ranking ability and highlight LLM-guided feature discovery as a promising approach to interpret and combine the outputs of computational chemistry tools.
#05Nov 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.