#01Nov 5, 2026
cs.LG
On the limitations of molecular representations
Acer Blake, Fergus Imrie, Charlotte M. Deane
Molecular representations such as fingerprints and learned embeddings play a central role in cheminformatics and small-molecule machine learning. They serve as the primary input for a diverse array of tasks, including clustering, dataset splitting, and virtual screening, yet their evaluation is often limited to downstream model performance on narrow benchmark tasks. We carried out a systematic investigation of the quality of molecular representations, finding that none of the state-of-the-art molecular embedding models capture graph structure, 3D shape, or ADMET endpoint similarity better than fingerprints or physicochemical descriptors. However, classical fingerprints also revealed their own material limitations. For example, we show that depending on the representation, between 225M and $\sim$4B molecules have non-unique representations in the 10.8B Enamine REAL database, with implications for virtual screening. Our findings provide an insight into the current limitations of molecular representations, outlining future research directions for the development of more robust encodings of small molecules.
#02Nov 5, 2026
cs.LG
Unpacking the Compute Efficiency of Strong-to-Weak OPD against GRPO
Zeyu Leo Liu, Yang Li, Bo Pang and 7 more
On-policy distillation (OPD) trains a student on its own rollouts under a frozen teacher's per-token supervision. Does this dense signal reduce the training FLOPs needed to reach a target accuracy compared with reinforcement learning? We systematically compare vanilla reverse-KL OPD with Group Relative Policy Optimization (GRPO) across task difficulty, student and teacher size, domain, and optimization choices, measuring held-out accuracy against training FLOPs. With an external post-trained teacher, OPD generally loses to GRPO in accuracy per training FLOP at matched settings, even when the teacher is further trained with GRPO, and often suffers response-length inflation. Yet a different teacher changes the picture: when the teacher is the student's own GRPO checkpoint, OPD recovers that checkpoint's accuracy on math with $50\times$ fewer distillation FLOPs than GRPO needs to reach the same accuracy. Following the same teacher setting, we consistently observe this high efficiency with a larger student, on code, and in a second model family. On a single domain, however, the GRPO checkpoint is already the desired model, so distilling it adds to total compute. Across domains, separate GRPO checkpoints hold different capabilities, and no single checkpoint serves every domain. Multi-teacher OPD (DeepSeek-AI, 2026) consolidates per-domain GRPO experts into a single student that matches each expert's accuracy, with the distillation stage costing only 5.2% (on 2 domains) and 8.0% (on 4 domains) of the specialist training FLOPs. Counting specialist training and distillation together, this pipeline reaches joint GRPO's performance on the 2-domain mix with 42.0% fewer total FLOPs.
#03Nov 5, 2026
cs.LG
Adversarial Training with Large Step Sizes: Implicit Bias, Optimization, and Sharpness
Yi Feng, Andrea Paudice
Adversarial Training (AT) is an important method for improving model robustness. We study the dynamics of deterministic Gradient Descent (GD) in AT. Most existing works in this direction focus on the small or vanishing step sizes regime, where GD resembles a continuous-time flow. However, such step sizes can make training inefficient and are rarely used in practice. In this paper, we study the AT dynamics of GD with large constant step sizes. We first study GD in adversarial linear logistic regression, focusing on two aspects: where the model parameters converge (implicit bias) and how quickly the losses decrease (optimization). We then turn to neural networks training and study how the sharpness of losses evolve during AT. Our results advance the understanding of the behaviors of GD with large step sizes in AT and highlight three key differences from its behavior in Standard Training (ST): (i) the implicit bias gap between AT and ST, previously established only for small step sizes, persists for arbitrarily large constant step sizes, (ii) different from ST, there is no uniform rate of convergence for the optimization error in AT, and (iii) sharpness can exhibit two-stage dynamics that differ from the Edge-of-Stability behavior observed in ST.
#04Nov 5, 2026
cs.CR
FedReason: Large Language Models as Weight-Space Meta-Aggregators for Heterogeneous Federated Learning
Ali Mohammadi Ruzbahani, Abbas Yazdinejad, Hadis Karimipour
Federated learning servers combine client models with a fixed aggregation rule, and each rule in common use is designed for one kind of heterogeneity. We study whether a large language model (LLM) that inspects the client models can choose the rule itself, without any training on the server. In FedReason, the LLM is called every ten rounds. It analyses the weights by running code in a restricted server-side sandbox, sees only the printed results, may score a few candidates on a 500-image proxy set, and submits a short Python aggregation program. The server applies the program until the next call and falls back to FedAvg whenever its output is invalid. Full weight tensors never leave the server. We evaluated FedReason with Claude Opus 5.5 on CIFAR-10 and CIFAR-100 with ResNet-18 under Dirichlet label skew, width-heterogeneous sub-models and Byzantine clients, in 168 runs against 14 baselines. Across 12 paired label-skew runs it beat FedAvg by 1.26 percentage points on average (10 wins), and a control that spends the same per-round proxy budget on choosing among standard rules by 1.08 points. It was the strongest server-side rule on CIFAR-100 but did not beat SCAFFOLD, which changes client training. With three of ten clients malicious, it excluded all sign-flipping clients from the first round and stayed about one point below FLTrust without training a root model. Without proxy feedback, accuracy fell from 73.8% to 38.8% in one seed. A 60-round run cost 0.79 USD in API fees on average.
#05Nov 5, 2026
cs.LG
Synthesis of Ovarian Cancer Multi-Omics Datasets: A Biology-Informed Evaluation Framework
Déborah Boyenval, Alina Malyutina, Jaana Oikkonen and 2 more
Paired multi-omic cancer cohorts are costly to assemble and difficult to share, motivating synthetic cohorts as a complementary resource. As generative model development accelerates, we shift the focus from proposing yet another architecture to defining evaluation criteria that determine whether synthetic data preserve biologically relevant structure. We introduce a biology-informed and patient-disjoint framework for evaluating the generation of paired RNA expression and copy-number variation (CNV) profiles, and apply it to the longitudinal DECIDER high-grade serous ovarian cancer cohort. The framework assesses modality-specific fidelity and coherence between RNA and CNV pairs using agreement between real training and held-out data as a reference, alongside complementary training-data proximity diagnostics. We adapt three multi-omic integration architectures based on variational autoencoders to generate paired profiles. The model leading several fidelity and coherence measures also shows the strongest training-data proximity. The protocol and case study offer the community a reference for comparing future multi-omic generators.