Daily Papers

Fine-grained manipulation couples instruction grounding, local visual precision, and sustained execution. We present FineCraft, a framework that adapts pretrained models for fine-grained manipulation in the MetaFine Challenge. A task-routed mixture of policies selects independently adapted DINOv2-DiT or pretrained π_{0.5} policies through a common observation-action interface. Local visual features help identify the instructed object parts, demonstrations and expert continuations teach the required actions, and new observations guide replanning during execution. FineCraft ranks fourth with an overall score of 0.878, exceeding the published reference on all five tasks. Official results and local diagnostics characterize performance across visual perturbations, instruction changes, and multi-stage manipulation. Code is available at https://github.com/eqcy/FineCraft

Meta-analysis is a demanding form of evidence synthesis that combines literature retrieval, PI/ECO-guided study selection, and statistical aggregation. Its structured, verifiable workflow makes it an ideal substrate for evaluating systematic scientific reasoning, yet existing benchmarks lack ground truth across the full retrieval-screening-synthesis pipeline. We introduce MetaSyn, a dataset of 442 expert-curated meta-analyses from Nature Portfolio journals. Each entry pairs a research question with PI/ECO criteria, a retrieval corpus of 140k PubMed articles, verified positive studies, hard negatives that are topically similar but PI/ECO-ineligible, and complete search strategies and date bounds. Benchmarking twelve pipeline configurations (nine RAG variants and a protocol-driven agent) reveals a critical screening bottleneck: despite a retrieval ceiling of 90.9% recall at K=200, no system recovers more than 52.7% of ground-truth included literature. Current LLMs fail to reliably separate eligible studies from PI/ECO-failing distractors in pools of comparable topical relevance. Stage-attributed metrics capture where systems succeed and fail; a single end-to-end score does not.

The discovery and identification of molecules in biological and environmental samples is crucial for advancing biomedical and chemical sciences. Tandem mass spectrometry (MS/MS) is the leading technique for high-throughput elucidation of molecular structures. However, decoding a molecular structure from its mass spectrum is exceptionally challenging, even when performed by human experts. As a result, the vast majority of acquired MS/MS spectra remain uninterpreted, thereby limiting our understanding of the underlying (bio)chemical processes. Despite decades of progress in machine learning applications for predicting molecular structures from MS/MS spectra, the development of new methods is severely hindered by the lack of standard datasets and evaluation protocols. To address this problem, we propose MassSpecGym -- the first comprehensive benchmark for the discovery and identification of molecules from MS/MS data. Our benchmark comprises the largest publicly available collection of high-quality labeled MS/MS spectra and defines three MS/MS annotation challenges: de novo molecular structure generation, molecule retrieval, and spectrum simulation. It includes new evaluation metrics and a generalization-demanding data split, therefore standardizing the MS/MS annotation tasks and rendering the problem accessible to the broad machine learning community. MassSpecGym is publicly available at https://github.com/pluskal-lab/MassSpecGym.

Molecular optimization seeks to improve a molecule through small structural edits while preserving similarity to the starting compound. Recent language-model approaches typically treat this task as prompt-conditioned sequence generation. However, relying on natural language introduces an inherent data-scaling bottleneck, often leads to chemical hallucinations, and ignores the strong context dependence of fragment effects. We present FORGE, a two-stage framework that reformulates molecular optimization as context-aware local editing. By utilizing automatically mined, verified low-to-high edit pairs instead of expensive human text annotations, Stage 1 ranks candidate fragments by their property contribution under the full molecular context to inject chemical prior, and Stage 2 generates explicit fragment replacements. Built on a compact 0.6B language model, FORGE further adapts to unseen black-box objectives through in-context demonstrations. Across Prompt-MolOpt, PMO-1k and ChemCoTBench, FORGE consistently outperforms prior methods, including substantially larger language models and graph methods. These results highlight the value of explicit fragment-level supervision as a more easily obtainable, scalable, and hallucination-less alternative to natural language training.

We introduce FragAtlas-62M, a specialized foundation model trained on the largest fragment dataset to date. Built on the complete ZINC-22 fragment subset comprising over 62 million molecules, it achieves unprecedented coverage of fragment chemical space. Our GPT-2 based model (42.7M parameters) generates 99.90% chemically valid fragments. Validation across 12 descriptors and three fingerprint methods shows generated fragments closely match the training distribution (all effect sizes < 0.4). The model retains 53.6% of known ZINC fragments while producing 22% novel structures with practical relevance. We release FragAtlas-62M with training code, preprocessed data, documentation, and model weights to accelerate adoption.

Identifying a small molecule from its mass spectrum is the primary open problem in computational metabolomics. This is typically cast as information retrieval: an unknown spectrum is matched against spectra predicted computationally from a large database of chemical structures. However, current approaches to spectrum prediction model the output space in ways that force a tradeoff between capturing high resolution mass information and tractable learning. We resolve this tradeoff by casting spectrum prediction as a mapping from an input molecular graph to a probability distribution over molecular formulas. We discover that a large corpus of mass spectra can be closely approximated using a fixed vocabulary constituting only 2% of all observed formulas. This enables efficient spectrum prediction using an architecture similar to graph classification - GrAFF-MS - achieving significantly lower prediction error and orders-of-magnitude faster runtime than state-of-the-art methods.

Building generalist models has recently demonstrated remarkable capabilities in diverse scientific domains. Within the realm of molecular learning, several studies have explored unifying diverse tasks across diverse domains. However, negative conflicts and interference between molecules and knowledge from different domain may have a worse impact in threefold. First, conflicting molecular representations can lead to optimization difficulties for the models. Second, mixing and scaling up training data across diverse tasks is inherently challenging. Third, the computational cost of refined pretraining is prohibitively high. To address these limitations, this paper presents Omni-Mol, a scalable and unified LLM-based framework for direct instruction tuning. Omni-Mol builds on three key components to tackles conflicts: (1) a unified encoding mechanism for any task input; (2) an active-learning-driven data selection strategy that significantly reduces dataset size; (3) a novel design of the adaptive gradient stabilization module and anchor-and-reconcile MoE framework that ensures stable convergence. Experimentally, Omni-Mol achieves state-of-the-art performance across 15 molecular tasks, demonstrates the presence of scaling laws in the molecular domain, and is supported by extensive ablation studies and analyses validating the effectiveness of its design. The code and weights of the powerful AI-driven chemistry generalist are open-sourced at: https://anonymous.4open.science/r/Omni-Mol-8EDB.

Meta-learning enables algorithms to quickly learn a newly encountered task with just a few labeled examples by transferring previously learned knowledge. However, the bottleneck of current meta-learning algorithms is the requirement of a large number of meta-training tasks, which may not be accessible in real-world scenarios. To address the challenge that available tasks may not densely sample the space of tasks, we propose to augment the task set through interpolation. By meta-learning with task interpolation (MLTI), our approach effectively generates additional tasks by randomly sampling a pair of tasks and interpolating the corresponding features and labels. Under both gradient-based and metric-based meta-learning settings, our theoretical analysis shows MLTI corresponds to a data-adaptive meta-regularization and further improves the generalization. Empirically, in our experiments on eight datasets from diverse domains including image recognition, pose prediction, molecule property prediction, and medical image classification, we find that the proposed general MLTI framework is compatible with representative meta-learning algorithms and consistently outperforms other state-of-the-art strategies.

Nuclear Magnetic Resonance (NMR) spectroscopy is the cornerstone of small-molecule structure elucidation. While deep learning has demonstrated significant potential in automating structure elucidation and spectral simulation, current progress is severely impeded by the reliance on synthetic datasets, which introduces significant domain shifts when applied to real-world experimental spectra. Furthermore, the lack of standardized evaluation protocols and rigorous data splitting strategies frequently leads to unfair comparisons and data leakage. To address these challenges, we introduce NMRGym, the largest and most comprehensive standardized dataset and benchmark derived from high-quality experimental NMR data to date. Comprising 269,999 unique molecules paired with high-fidelity ^1H and ^{13}C spectra, NMRGym bridges the critical gap between synthetic approximations and real-world diversity. We implement a strict quality control pipeline and unify data formats to ensure fair comparison. To strictly prevent data leakage, we enforce a scaffold-based split. Additionally, we provide fine-grained peak-atom level annotations to support future usage. Leveraging this resource, we establish a comprehensive evaluation suite covering diverse downstream tasks, including structure elucidation, functional group prediction from NMR, toxicity prediction from NMR, and spectral simulation, benchmarking representative state-of-the-art methodologies. Finally, we release an open-source leadboard with an automated leaderboard to foster community collaboration and standardize future research. The dataset, benchmark and leaderboard are publicly available at blue{https://AIMS-Lab-HKUSTGZ.github.io/NMRGym/}.

Generative molecular design is shaped by simple proxy benchmarks for drug-like properties and models pretrained on large pharmaceutical datasets. This combination yields strong benchmark metrics but limits transferability to domains structurally distinct from drug discovery. To overcome this limitation and drive discovery toward real, scientifically grounded targets, we introduce the Nanotechnology Molecular Optimization (NMO) Benchmark, which bridges machine learning (ML) and quantum materials science. NMO acts simultaneously as a rigorous testbed for the ML community and a discovery engine for nanotechnology research. The suite replaces proxy oracles with quantum simulations and introduces strict protocols that prioritize scientific utility over leaderboard-oriented overfitting. The physics-based NMO tasks impose hard structural constraints and rugged fitness landscapes, posing fundamentally new requirements on generative models. Notably, advanced molecular optimization methods underperform much simpler approaches on the NMO tasks. We develop a new baseline method identifying the critical components to solve the NMO tasks, including a novel representation for modeling structural constraints and a domain-agnostic pretraining strategy to eliminate pharmaceutical dataset bias. Our results surpass state-of-the-art physical properties and reveal previously unknown structural motifs, offering new insights for the nanotechnology community and demonstrating that ML can drive genuine scientific discovery.

The annotation (assigning structural chemical identities) of MS/MS spectra remains a significant challenge due to the enormous molecular diversity in biological samples and the limited scope of reference databases. Currently, the vast majority of spectral measurements remain in the "dark chemical space" without structural annotations. To improve annotation, we propose MADGEN (Mass-spec Attends to De Novo Molecular GENeration), a scaffold-based method for de novo molecular structure generation guided by mass spectrometry data. MADGEN operates in two stages: scaffold retrieval and spectra-conditioned molecular generation starting with the scaffold. In the first stage, given an MS/MS spectrum, we formulate scaffold retrieval as a ranking problem and employ contrastive learning to align mass spectra with candidate molecular scaffolds. In the second stage, starting from the retrieved scaffold, we employ the MS/MS spectrum to guide an attention-based generative model to generate the final molecule. Our approach constrains the molecular generation search space, reducing its complexity and improving generation accuracy. We evaluate MADGEN on three datasets (NIST23, CANOPUS, and MassSpecGym) and evaluate MADGEN's performance with a predictive scaffold retriever and with an oracle retriever. We demonstrate the effectiveness of using attention to integrate spectral information throughout the generation process to achieve strong results with the oracle retriever.

Machine learning (ML) models hold the promise of transforming atomic simulations by delivering quantum chemical accuracy at a fraction of the computational cost. Realization of this potential would enable high-throughout, high-accuracy molecular screening campaigns to explore vast regions of chemical space and facilitate ab initio simulations at sizes and time scales that were previously inaccessible. However, a fundamental challenge to creating ML models that perform well across molecular chemistry is the lack of comprehensive data for training. Despite substantial efforts in data generation, no large-scale molecular dataset exists that combines broad chemical diversity with a high level of accuracy. To address this gap, Meta FAIR introduces Open Molecules 2025 (OMol25), a large-scale dataset composed of more than 100 million density functional theory (DFT) calculations at the omegaB97M-V/def2-TZVPD level of theory, representing billions of CPU core-hours of compute. OMol25 uniquely blends elemental, chemical, and structural diversity including: 83 elements, a wide-range of intra- and intermolecular interactions, explicit solvation, variable charge/spin, conformers, and reactive structures. There are ~83M unique molecular systems in OMol25 covering small molecules, biomolecules, metal complexes, and electrolytes, including structures obtained from existing datasets. OMol25 also greatly expands on the size of systems typically included in DFT datasets, with systems of up to 350 atoms. In addition to the public release of the data, we provide baseline models and a comprehensive set of model evaluations to encourage community engagement in developing the next-generation ML models for molecular chemistry.

Adapting machine-learned interatomic potential (MLIP) foundation models to specialised tasks through fine-tuning is an increasingly important practice, yet systematic guidance on when and how to fine-tune is currently limited. We evaluate seven fine-tuning strategies -- naive full-parameter updates, two layer-freezing variants, Low-Rank Adaptation (LoRA), multihead replay, pseudolabelled replay, and replay combined with LoRA -- across five chemically diverse benchmarks (aqueous NaCl, ice polymorphs, S_N2 reactions, SPICE biomolecules, and lithium electrolytes), three generations of foundation models, and training sets spanning five orders of magnitude. To support this evaluation we implement three capabilities in the MACE codebase: LoRA adapted for equivariant message-passing architectures, including both scalar and equivariant linear layers; pseudolabelled replay, which decouples the replay data source from the original pretraining corpus; and model-aware atomic reference energy (E0) reestimation for fine-tuning workflows. We find that foundation model quality, correct E0 initialisation, and well-chosen hyperparameters are prerequisites whose impact routinely exceeds that of the fine-tuning strategy itself. Once these prerequisites are met, most strategies achieve strong target-task accuracy, consistently surpassing models trained from scratch. The practical distinction depends on deployment scope: naive fine-tuning offers the best convergence for single-system applications, while multihead replay -- with either original or pseudolabelled data -- is the only approach tested that consistently preserves out-of-distribution robustness, maintaining both pretraining-distribution accuracy for broader deployment and many-body short-range repulsion.

Reliable benchmarking is critical for developing machine learning models for tandem mass spectrometry (MS/MS) based molecule discovery. Subtle issues in experimental design and model evaluation procedures can degrade the trustworthiness of such benchmarks and lead to erroneous conclusions. We conduct a thorough review of model evaluation issues in the recent MS/MS machine learning literature, using the standard MassSpecGym benchmark suite as a case study to illustrate the impact of these issues. We find evaluation issues in at least 17 of 26 papers reporting MassSpecGym benchmark results in the first year of its adoption. We isolate three classes of failures: (i) data leakage, (ii) shortcut learning, and (iii) implementation bugs and metric divergence. Through extensive experimentation and code replication, we quantify the impact of these issues and show how they corrupt the evaluation standards MassSpecGym was designed to enforce. We distill our findings into recommendations generalizable to MS/MS challenges, benchmarks, and custom evaluation setups. We also release MassSpecGym v1.5, an implementation of our recommendations in the MassSpecGym benchmarking suite which addresses the failure modes identified in this audit. MassSpecGym v1.5 is publicly available at https://github.com/pluskal-lab/MassSpecGym.

Molecular optimization, which transforms a given input molecule X into another Y with desirable properties, is essential in molecular drug discovery. The traditional translating approaches, generating the molecular graphs from scratch by adding some substructures piece by piece, prone to error because of the large set of candidate substructures in a large number of steps to the final target. In this study, we present a novel molecular optimization paradigm, Graph Polish, which changes molecular optimization from the traditional "two-language translating" task into a "single-language polishing" task. The key to this optimization paradigm is to find an optimization center subject to the conditions that the preserved areas around it ought to be maximized and thereafter the removed and added regions should be minimized. We then propose an effective and efficient learning framework T&S polish to capture the long-term dependencies in the optimization steps. The T component automatically identifies and annotates the optimization centers and the preservation, removal and addition of some parts of the molecule, and the S component learns these behaviors and applies these actions to a new molecule. Furthermore, the proposed paradigm can offer an intuitive interpretation for each molecular optimization result. Experiments with multiple optimization tasks are conducted on four benchmark datasets. The proposed T&S polish approach achieves significant advantage over the five state-of-the-art baseline methods on all the tasks. In addition, extensive studies are conducted to validate the effectiveness, explainability and time saving of the novel optimization paradigm.

In biological tasks, data is rarely plentiful as it is generated from hard-to-gather measurements. Therefore, pre-training foundation models on large quantities of available data and then transfer to low-data downstream tasks is a promising direction. However, how to design effective foundation models for molecular learning remains an open question, with existing approaches typically focusing on models with large parameter capacities. In this work, we propose MiniMol, a foundational model for molecular learning with 10 million parameters. MiniMol is pre-trained on a mix of roughly 3300 sparsely defined graph- and node-level tasks of both quantum and biological nature. The pre-training dataset includes approximately 6 million molecules and 500 million labels. To demonstrate the generalizability of MiniMol across tasks, we evaluate it on downstream tasks from the Therapeutic Data Commons (TDC) ADMET group showing significant improvements over the prior state-of-the-art foundation model across 17 tasks. MiniMol will be a public and open-sourced model for future research.

Large Language Models like ChatGPT demonstrate a remarkable capacity to learn new concepts during inference without any fine-tuning. However, visual models trained to detect new objects during inference have been unable to replicate this ability, and instead either perform poorly or require meta-training and/or fine-tuning on similar objects. In this work, we propose a meta-learning algorithm that emulates Large Language Models by learning new visual concepts during inference without fine-tuning. Our approach leverages a frozen pre-trained feature extractor, and analogous to in-context learning, recasts meta-learning as sequence modeling over datapoints with known labels and a test datapoint with an unknown label. On 8 out of 11 meta-learning benchmarks, our approach -- without meta-training or fine-tuning -- exceeds or matches the state-of-the-art algorithm, P>M>F, which is meta-trained on these benchmarks.

The rapid advancement in artificial intelligence and natural language processing has led to the development of large-scale datasets aimed at benchmarking the performance of machine learning models. Herein, we introduce 'RetChemQA,' a comprehensive benchmark dataset designed to evaluate the capabilities of such models in the domain of reticular chemistry. This dataset includes both single-hop and multi-hop question-answer pairs, encompassing approximately 45,000 Q&As for each type. The questions have been extracted from an extensive corpus of literature containing about 2,530 research papers from publishers including NAS, ACS, RSC, Elsevier, and Nature Publishing Group, among others. The dataset has been generated using OpenAI's GPT-4 Turbo, a cutting-edge model known for its exceptional language understanding and generation capabilities. In addition to the Q&A dataset, we also release a dataset of synthesis conditions extracted from the corpus of literature used in this study. The aim of RetChemQA is to provide a robust platform for the development and evaluation of advanced machine learning algorithms, particularly for the reticular chemistry community. The dataset is structured to reflect the complexities and nuances of real-world scientific discourse, thereby enabling nuanced performance assessments across a variety of tasks. The dataset is available at the following link: https://github.com/nakulrampal/RetChemQA

Metasurfaces are ultrathin, engineered materials composed of nanostructures that manipulate light in ways unattainable by natural materials. Recent advances have leveraged computational optimization, machine learning, and deep learning to automate their design. However, existing approaches exhibit two fundamental limitations: (1) they often restrict the model to generating only a subset of design parameters, and (2) they rely on heavily downsampled spectral targets, which compromises both the novelty and accuracy of the resulting structures. The core challenge lies in developing a generative model capable of exploring a large, unconstrained design space while precisely capturing the intricate physical relationships between material parameters and their high-resolution spectral responses. In this paper, we introduce MetaDiT, a novel framework for high-fidelity metasurface design that addresses these limitations. Our approach leverages a robust spectrum encoder pretrained with contrastive learning, providing strong conditional guidance to a Diffusion Transformer-based backbone. Experiments demonstrate that MetaDiT outperforms existing baselines in spectral accuracy, we further validate our method through extensive ablation studies. Our code and model weights will be open-sourced to facilitate future research.

Nuclear Magnetic Resonance (NMR) spectroscopy is one of the most powerful and widely used tools for molecular structure elucidation in organic chemistry. However, the interpretation of NMR spectra to determine unknown molecular structures remains a labor-intensive and expertise-dependent process, particularly for complex or novel compounds. Although recent methods have been proposed for molecular structure elucidation, they often underperform in real-world applications due to inherent algorithmic limitations and limited high-quality data. Here, we present NMR-Solver, a practical and interpretable framework for the automated determination of small organic molecule structures from ^1H and ^{13}C NMR spectra. Our method introduces an automated framework for molecular structure elucidation, integrating large-scale spectral matching with physics-guided fragment-based optimization that exploits atomic-level structure-spectrum relationships in NMR. We evaluate NMR-Solver on simulated benchmarks, curated experimental data from the literature, and real-world experiments, demonstrating its strong generalization, robustness, and practical utility in challenging, real-life scenarios. NMR-Solver unifies computational NMR analysis, deep learning, and interpretable chemical reasoning into a coherent system. By incorporating the physical principles of NMR into molecular optimization, it enables scalable, automated, and chemically meaningful molecular identification, establishing a generalizable paradigm for solving inverse problems in molecular science.

Reaction data underpin machine learning for reaction prediction, condition recommendation, and retrosynthetic planning, yet extracting these data from literature figures still requires substantial manual effort. Many figures encode multiple experiments through shared templates, substituent tables, and product grids. Recovering concrete reaction records therefore requires molecular recognition, association of evidence with individual experimental entries, and reconstruction of indirectly specified participants. We present RxnMiner, a multimodal agent system that combines an expert-informed extraction procedure with a chemistry toolbox to coordinate these operations. The agent reads molecular structures, resolves shared and entry-specific evidence, and instantiates participants from templates to assemble source-linked reaction records. We also introduce ChemRxn-Bench, a benchmark of 603 reaction figures with 8,547 manually annotated and reviewed reaction records, evaluated under a common protocol for exact molecular identity and reactant-product pairing. On this benchmark, with Qwen3.8-Flash-Next as the backbone, RxnMiner raises stereochemistry-aware reaction macro-F1 from 21.0% under direct prediction to 71.0%, compared with 25.0% for the strongest existing extraction system. Across five backbones, it also outperforms the same base agent without the extraction procedure and chemistry toolbox by 9.4 to 25.5 points. Applied without human intervention to 10,107 literature figures, RxnMiner produces a silver corpus of 88,202 source-linked reaction records.

Metamaterials, engineered materials with architected structures across multiple length scales, offer unprecedented and tunable mechanical properties that surpass those of conventional materials. However, leveraging advanced machine learning (ML) for metamaterial discovery is hindered by three fundamental challenges: (C1) Data Heterogeneity Challenge arises from heterogeneous data sources, heterogeneous composition scales, and heterogeneous structure categories; (C2) Model Complexity Challenge stems from the intricate geometric constraints of ML models, which complicate their adaptation to metamaterial structures; and (C3) Human-AI Collaboration Challenge comes from the "dual black-box'' nature of sophisticated ML models and the need for intuitive user interfaces. To tackle these challenges, we introduce a unified framework, named MetamatBench, that operates on three levels. (1) At the data level, we integrate and standardize 5 heterogeneous, multi-modal metamaterial datasets. (2) The ML level provides a comprehensive toolkit that adapts 17 state-of-the-art ML methods for metamaterial discovery. It also includes a comprehensive evaluation suite with 12 novel performance metrics with finite element-based assessments to ensure accurate and reliable model validation. (3) The user level features a visual-interactive interface that bridges the gap between complex ML techniques and non-ML researchers, advancing property prediction and inverse design of metamaterials for research and applications. MetamatBench offers a unified platform deployed at http://zhoulab-1.cs.vt.edu:5550 that enables machine learning researchers and practitioners to develop and evaluate new methodologies in metamaterial discovery. For accessibility and reproducibility, we open-source our benchmark and the codebase at https://github.com/cjpcool/Metamaterial-Benchmark.

In this paper, we propose Text-based Open Molecule Generation Benchmark (TOMG-Bench), the first benchmark to evaluate the open-domain molecule generation capability of LLMs. TOMG-Bench encompasses a dataset of three major tasks: molecule editing (MolEdit), molecule optimization (MolOpt), and customized molecule generation (MolCustom). Each task further contains three subtasks, with each subtask comprising 5,000 test samples. Given the inherent complexity of open molecule generation, we have also developed an automated evaluation system that helps measure both the quality and the accuracy of the generated molecules. Our comprehensive benchmarking of 25 LLMs reveals the current limitations and potential areas for improvement in text-guided molecule discovery. Furthermore, with the assistance of OpenMolIns, a specialized instruction tuning dataset proposed for solving challenges raised by TOMG-Bench, Llama3.1-8B could outperform all the open-source general LLMs, even surpassing GPT-3.5-turbo by 46.5\% on TOMG-Bench. Our codes and datasets are available through https://github.com/phenixace/TOMG-Bench.

Large pre-trained language models (LMs) such as GPT-3 have acquired a surprising ability to perform zero-shot learning. For example, to classify sentiment without any training examples, we can "prompt" the LM with the review and the label description "Does the user like this movie?", and ask whether the next word is "yes" or "no". However, the next word prediction training objective is still misaligned with the target zero-shot learning objective. To address this weakness, we propose meta-tuning, which directly optimizes the zero-shot learning objective by fine-tuning pre-trained language models on a collection of datasets. We focus on classification tasks, and construct the meta-dataset by aggregating 43 existing datasets and annotating 441 label descriptions in a question-answering (QA) format. When evaluated on unseen tasks, meta-tuned models outperform a same-sized QA model and the previous SOTA zero-shot learning system based on natural language inference. Additionally, increasing parameter count from 220M to 770M improves AUC-ROC scores by 6.3%, and we forecast that even larger models would perform better. Therefore, measuring zero-shot learning performance on language models out-of-the-box might underestimate their true potential, and community-wide efforts on aggregating datasets and unifying their formats can help build models that answer prompts better.

Current AI benchmarks evaluate agents on task execution within human-designed workflows. These evaluations fundamentally fail to measure a critical next-level capability: whether models can autonomously develop agent systems. We introduce the Meta-Agent Challenge (MAC), an evaluation framework designed to test the capacity of frontier models for autonomous agent development. Specifically, a code agent (the meta-agent) is given a sandboxed environment, an evaluation API, and a time limitation to iteratively program an agent artifact that maximizes performance on a held-out test set across five domains. To ensure evaluation integrity, this framework is secured by multi-layer defenses against reward hacking. Leveraging this framework, we demonstrate that meta-agents rarely match human-engineered baseline policies, and the few that do are dominated by proprietary frontier models. Moreover, the design process exhibits high variance, and high optimization pressure surfaces emergent adversarial behaviors like ground-truth exfiltration-highlighting critical deficits in both robustness and model alignment. Ultimately, MAC provides a rigorous, open-source benchmark for autonomous AI research and development, offering an empirical proxy for evaluating recursive self-improvement. Benchmark is publicly available at: https://github.com/ant-research/meta-agent-challenge.

Generating molecules that satisfy precise numeric constraints over multiple physicochemical properties is critical and challenging. Although large language models (LLMs) are expressive, they struggle with precise multi-objective control and numeric reasoning without external structure and feedback. We introduce M olGen, a fragment-level, retrieval-augmented, two-stage framework for molecule generation under multi-property constraints. Stage I : Prototype generation: a multi-agent reasoner performs retrieval-anchored, fragment-level edits to produce a candidate near the feasible region. Stage II : RL-based fine-grained optimization: a fragment-level optimizer trained with Group Relative Policy Optimization (GRPO) applies one- or multi-hop refinements to explicitly minimize the property errors toward our target while regulating edit complexity and deviation from the prototype. A large, automatically curated dataset with reasoning chains of fragment edits and measured property deltas underpins both stages, enabling deterministic, reproducible supervision and controllable multi-hop reasoning. Unlike prior work, our framework better reasons about molecules by leveraging fragments and supports controllable refinement toward numeric targets. Experiments on generation under two sets of property constraints (QED, LogP, Molecular Weight and HOMO, LUMO) show consistent gains in validity and precise satisfaction of multi-property targets, outperforming strong LLMs and graph-based algorithms.

Molecular structure elucidation involves deducing a molecule's structure from various types of spectral data, which is crucial in chemical experimental analysis. While large language models (LLMs) have shown remarkable proficiency in analyzing and reasoning through complex tasks, they still encounter substantial challenges in molecular structure elucidation. We identify that these challenges largely stem from LLMs' limited grasp of specialized chemical knowledge. In this work, we introduce a Knowledge-enhanced reasoning framework for Molecular Structure Elucidation (K-MSE), leveraging Monte Carlo Tree Search for test-time scaling as a plugin. Specifically, we construct an external molecular substructure knowledge base to extend the LLMs' coverage of the chemical structure space. Furthermore, we design a specialized molecule-spectrum scorer to act as a reward model for the reasoning process, addressing the issue of inaccurate solution evaluation in LLMs. Experimental results show that our approach significantly boosts performance, particularly gaining more than 20% improvement on both GPT-4o-mini and GPT-4o. Our code is available at https://github.com/HICAI-ZJU/K-MSE.

Recent progress has expanded the use of large language models (LLMs) in drug discovery, including synthesis planning. However, objective evaluation of retrosynthesis performance remains limited. Existing benchmarks and metrics typically rely on published synthetic procedures and Top-K accuracy based on single ground-truth, which does not capture the open-ended nature of real-world synthesis planning. We propose a new benchmarking framework for single-step retrosynthesis that evaluates both general-purpose and chemistry-specialized LLMs using ChemCensor, a novel metric for chemical plausibility. By emphasizing plausibility over exact match, this approach better aligns with human synthesis planning practices. We also introduce CREED, a novel dataset comprising millions of ChemCensor-validated reaction records for LLM training, and use it to train a model that improves over the LLM baselines under this benchmark.

Bioassay activity prediction is often data-limited because drug-discovery datasets rely on time-consuming and expensive wet-lab experiments for data generation and evaluation. This challenge has inspired recent research into molecular foundation models (MFMs), which aim to encode general-purpose chemical knowledge into molecular representations that generalize well in data-constrained scenarios. This paper presents Monroe, a new MFM with several innovations over the existing state of the art: increased scale allowing pre-training on over 81 million molecules from the PM6 quantum chemistry dataset; improved graph representation of stereochemistry; improved training losses including conformer denoising and embedding decorrelation; improved multi-task learning; and the use of a prior-data-fitted model (TabPFN) for downstream in-context prediction. Our evaluations use a principled pairwise comparison framework that measures statistically significant performance differences. Across established Polaris benchmarks, Monroe matches or exceeds existing MFMs, while on activity cliff benchmarks, designed to assess utility for molecular discovery, it achieves significant improvements over prior methods. Finally, ablation and transfer experiments show that PFN-based downstream predictors also substantially improve two leading existing models, MiniMol and CheMeleon, yielding new state-of-the-art variants we call MiniMol_PFN and CheMeleon_PFN, suggesting that our downstream adaptation strategy generalizes beyond Monroe. Source code is at github.com/blazejba/monroe.

Molecular structure elucidation from tandem mass spectra (MS/MS) is a central inverse problem in analytical chemistry. Most existing approaches to MS/MS identification remain tied to reference libraries or predefined candidate sets, whereas de novo methods aim to generate structures directly from spectra. A common de novo route predicts a molecular fingerprint from the spectrum and then decodes structures from it, enabling decoder pretraining on large molecule-only corpora. However, this paradigm creates a training-inference mismatch: the decoder is trained on oracle fingerprints computed from molecules, but at inference it is queried with a noisy spectrum-induced fingerprint posterior that is typically collapsed to a single thresholded fingerprint. We introduce MS-GPT, which recasts fingerprint-mediated de novo elucidation as spectrum-induced posterior querying of a conditional molecule-language model. MS-GPT conditions a molecule-language model on fingerprints and formulas, then converts the spectrum-induced posterior into a band of fingerprint queries near the oracle-fingerprint manifold through active-bit density calibration. Candidates sampled across this band are pooled and ranked by generation-frequency consensus. A lightweight LoRA adapter further mitigates domain-specific posterior bias while preserving the pretrained molecular prior. On NPLIB1 and MassSpecGym, MS-GPT sets a new state of the art, reaching Top-1/Top-10 exact-match accuracy of 29.8\%/41.1\% and 23.9\%/28.7\%, respectively. Candidate-pool scaling shows that efficient autoregressive molecular generation continues to improve recall with a little additional inference cost. The source code and model checkpoints are available at https://github.com/VIKI623/MS-GPT.

While the OneRec series has successfully unified the fragmented recommendation pipeline into an end-to-end generative framework, a significant gap remains between recommendation systems and general intelligence. Constrained by isolated data, they operate as domain specialists-proficient in pattern matching but lacking world knowledge, reasoning capabilities, and instruction following. This limitation is further compounded by the lack of a holistic benchmark to evaluate such integrated capabilities. To address this, our contributions are: 1) RecIF Bench & Open Data: We propose RecIF-Bench, a holistic benchmark covering 8 diverse tasks that thoroughly evaluate capabilities from fundamental prediction to complex reasoning. Concurrently, we release a massive training dataset comprising 96 million interactions from 160,000 users to facilitate reproducible research. 2) Framework & Scaling: To ensure full reproducibility, we open-source our comprehensive training pipeline, encompassing data processing, co-pretraining, and post-training. Leveraging this framework, we demonstrate that recommendation capabilities can scale predictably while mitigating catastrophic forgetting of general knowledge. 3) OneRec-Foundation: We release OneRec Foundation (1.7B and 8B), a family of models establishing new state-of-the-art (SOTA) results across all tasks in RecIF-Bench. Furthermore, when transferred to the Amazon benchmark, our models surpass the strongest baselines with an average 26.8% improvement in Recall@10 across 10 diverse datasets (Figure 1). This work marks a step towards building truly intelligent recommender systems. Nonetheless, realizing this vision presents significant technical and theoretical challenges, highlighting the need for broader research engagement in this promising direction.

Foundation models have been transformational in machine learning fields such as natural language processing and computer vision. Similar success in atomic property prediction has been limited due to the challenges of training effective models across multiple chemical domains. To address this, we introduce Joint Multi-domain Pre-training (JMP), a supervised pre-training strategy that simultaneously trains on multiple datasets from different chemical domains, treating each dataset as a unique pre-training task within a multi-task framework. Our combined training dataset consists of sim120M systems from OC20, OC22, ANI-1x, and Transition-1x. We evaluate performance and generalization by fine-tuning over a diverse set of downstream tasks and datasets including: QM9, rMD17, MatBench, QMOF, SPICE, and MD22. JMP demonstrates an average improvement of 59% over training from scratch, and matches or sets state-of-the-art on 34 out of 40 tasks. Our work highlights the potential of pre-training strategies that utilize diverse data to advance property prediction across chemical domains, especially for low-data tasks.

Traditional AI methods often rely on task-specific model designs and training, which constrain both the scalability of model size and generalization across different tasks. Here, we introduce ChemFM, a large foundation model specifically developed for chemicals. By conducting a series of scaling experiments, we identify UniChem as the informative molecular database for pre-training the foundation model. ChemFM comprises 3 billion parameters and is pre-trained on 178 million molecules using self-supervised causal language modeling to extract generalizable molecular representations. This model can be adapted to diverse downstream chemical applications using either full-parameter or parameter-efficient fine-tuning methods. ChemFM consistently outperforms state-of-the-art task-specific AI models across all tested tasks. Notably, it achieves up to 67.48% performance improvement across 34 property prediction benchmarks, up to 33.80% reduction in mean average deviation between conditioned and actual properties of generated molecules in conditional molecular generation tasks, and up to 3.7% top-1 accuracy improvement across 4 reaction prediction datasets. Moreover, ChemFM demonstrates its superior performance in predicting antibiotic activity and cytotoxicity, highlighting its potential to advance the discovery of novel antibiotics. Furthermore, we demonstrate that, as a foundation model, ChemFM exhibits strong data efficiency, requiring significantly fewer labeled training samples to achieve state-of-the-art performance. We anticipate that ChemFM will significantly advance chemistry research by providing a foundation model capable of effectively generalizing across a broad range of tasks with minimal additional training.

Progress in computer-aided synthesis planning (CASP) is obscured by the lack of standardized evaluation infrastructure and the reliance on metrics that prioritize topological completion over chemical validity. We introduce RetroCast, a unified evaluation suite that standardizes heterogeneous model outputs into a common schema to enable statistically rigorous, apples-to-apples comparison. The framework includes a reproducible benchmarking pipeline with stratified sampling and bootstrapped confidence intervals, accompanied by SynthArena, an interactive platform for qualitative route inspection. We utilize this infrastructure to evaluate leading search-based and sequence-based algorithms on a new suite of standardized benchmarks. Our analysis reveals a divergence between "solvability" (stock-termination rate) and route quality; high solvability scores often mask chemical invalidity or fail to correlate with the reproduction of experimental ground truths. Furthermore, we identify a "complexity cliff" in which search-based methods, despite high solvability rates, exhibit a sharp performance decay in reconstructing long-range synthetic plans compared to sequence-based approaches. We release the full framework, benchmark definitions, and a standardized database of model predictions to support transparent and reproducible development in the field.

Current benchmarks for evaluating the chemical reasoning capabilities of Large Language Models (LLMs) are limited by oversimplified tasks, lack of process-level evaluation, and misalignment with expert-level chemistry skills. To address these issues, we introduce SUPERChem, a benchmark of 500 expert-curated reasoning-intensive chemistry problems, covering diverse subfields and provided in both multimodal and text-only formats. Original content and an iterative curation pipeline eliminate flawed items and mitigate data contamination. Each problem is paired with an expert-authored solution path, enabling Reasoning Path Fidelity (RPF) scoring to evaluate reasoning quality beyond final-answer accuracy. Evaluations against a human baseline of 40.3% accuracy show that even the best-performing model, GPT-5 (High), reaches only 38.5%, followed closely by Gemini 2.5 Pro (37.9%) and DeepSeek-V3.1-Think (37.3%). SUPERChem elicits multi-step, multimodal reasoning, reveals model-dependent effects of visual information, and distinguishes high-fidelity reasoners from heuristic ones. By providing a challenging benchmark and a reliable evaluation framework, SUPERChem aims to facilitate the advancement of LLMs toward expert-level chemical intelligence. The dataset of the benchmark is available at https://huggingface.co/datasets/ZehuaZhao/SUPERChem.

Machine learning force fields (MLFF) have been proposed to accelerate molecular dynamics (MD) simulation, which finds widespread applications in chemistry and biomedical research. Even for the most data-efficient MLFFs, reaching chemical accuracy can require hundreds of frames of force and energy labels generated by expensive quantum mechanical algorithms, which may scale as O(n^3) to O(n^7), with n proportional to the number of basis functions. To address this issue, we propose a multi-stage computational framework -- ASTEROID, which lowers the data cost of MLFFs by leveraging a combination of cheap inaccurate data and expensive accurate data. The motivation behind ASTEROID is that inaccurate data, though incurring large bias, can help capture the sophisticated structures of the underlying force field. Therefore, we first train a MLFF model on a large amount of inaccurate training data, employing a bias-aware loss function to prevent the model from overfitting tahe potential bias of this data. We then fine-tune the obtained model using a small amount of accurate training data, which preserves the knowledge learned from the inaccurate training data while significantly improving the model's accuracy. Moreover, we propose a variant of ASTEROID based on score matching for the setting where the inaccurate training data are unlabeled. Extensive experiments on MD datasets and downstream tasks validate the efficacy of ASTEROID. Our code and data are available at https://github.com/abukharin3/asteroid.

Molecular property prediction is crucial for drug discovery and materials science, yet existing approaches suffer from limited interpretability, poor cross-task generalization, and lack of chemical reasoning capabilities. Traditional machine learning models struggle with task transferability, while specialized molecular language models provide little insight into their decision-making processes. To address these limitations, we propose MPPReasoner, a multimodal large language model that incorporates chemical reasoning for molecular property prediction. Our approach, built upon Qwen2.5-VL-7B-Instruct, integrates molecular images with SMILES strings to enable comprehensive molecular understanding. We develop a two-stage training strategy: supervised fine-tuning (SFT) using 16,000 high-quality reasoning trajectories generated through expert knowledge and multiple teacher models, followed by Reinforcement Learning from Principle-Guided Rewards (RLPGR). RLPGR employs verifiable, rule-based rewards that systematically evaluate chemical principle application, molecular structure analysis, and logical consistency through computational verification. Extensive experiments across 8 datasets demonstrate significant performance improvements, with MPPReasoner outperforming the best baselines by 7.91\% and 4.53\% on in-distribution and out-of-distribution tasks respectively. MPPReasoner exhibits exceptional cross-task generalization and generates chemically sound reasoning paths that provide valuable insights into molecular property analysis, substantially enhancing both interpretability and practical utility for chemists. Code is available at https://anonymous.4open.science/r/MPPReasoner-12687.

While various models and computational tools have been proposed for structure and property analysis of molecules, generating molecules that conform to all desired structures and properties remains a challenge. Here, we introduce a multi-constraint molecular generation large language model, TSMMG, which, akin to a student, incorporates knowledge from various small models and tools, namely, the 'teachers'. To train TSMMG, we construct a large set of text-molecule pairs by extracting molecular knowledge from these 'teachers', enabling it to generate novel molecules that conform to the descriptions through various text prompts. We experimentally show that TSMMG remarkably performs in generating molecules meeting complex, natural language-described property requirements across two-, three-, and four-constraint tasks, with an average molecular validity of over 99% and success ratio of 82.58%, 68.03%, and 67.48%, respectively. The model also exhibits adaptability through zero-shot testing, creating molecules that satisfy combinations of properties that have not been encountered. It can comprehend text inputs with various language styles, extending beyond the confines of outlined prompts, as confirmed through empirical validation. Additionally, the knowledge distillation feature of TSMMG contributes to the continuous enhancement of small models, while the innovative approach to dataset construction effectively addresses the issues of data scarcity and quality, which positions TSMMG as a promising tool in the domains of drug discovery and materials science.

The ability to discover new materials with desirable properties is critical for numerous applications from helping mitigate climate change to advances in next generation computing hardware. AI has the potential to accelerate materials discovery and design by more effectively exploring the chemical space compared to other computational methods or by trial-and-error. While substantial progress has been made on AI for materials data, benchmarks, and models, a barrier that has emerged is the lack of publicly available training data and open pre-trained models. To address this, we present a Meta FAIR release of the Open Materials 2024 (OMat24) large-scale open dataset and an accompanying set of pre-trained models. OMat24 contains over 110 million density functional theory (DFT) calculations focused on structural and compositional diversity. Our EquiformerV2 models achieve state-of-the-art performance on the Matbench Discovery leaderboard and are capable of predicting ground-state stability and formation energies to an F1 score above 0.9 and an accuracy of 20 meV/atom, respectively. We explore the impact of model size, auxiliary denoising objectives, and fine-tuning on performance across a range of datasets including OMat24, MPtraj, and Alexandria. The open release of the OMat24 dataset and models enables the research community to build upon our efforts and drive further advancements in AI-assisted materials science.

The goal of meta-learning is to learn to adapt to a new task with only a few labeled examples. To tackle this problem in NLP, we propose in-context tuning, which recasts adaptation and prediction as a simple sequence prediction problem: to form the input sequence, we concatenate the task instruction, the labeled examples, and the target input to predict; to meta-train the model to learn from in-context examples, we fine-tune a pre-trained language model (LM) to predict the target label from the input sequences on a collection of tasks. We benchmark our method on two collections of text classification tasks: LAMA and BinaryClfs. Compared to first-order MAML which adapts the model with gradient descent, our method better leverages the inductive bias of LMs to perform pattern matching, and outperforms MAML by an absolute 6% AUC ROC score on BinaryClfs, with increasing advantage w.r.t. model size. Compared to non-fine-tuned in-context learning (i.e. prompting a raw LM), in-context tuning directly learns to learn from in-context examples. On BinaryClfs, in-context tuning improves the average AUC-ROC score by an absolute 10%, and reduces the variance with respect to example ordering by 6x and example choices by 2x.

Metabolomics knowledge is distributed across heterogeneous resources and remains difficult to translate into predictive representations. We developed MetaboLLM, a metabolomics-specialized large language model adapted through continual pretraining, supervised fine-tuning, and structured retrieval, together with MetaboLLM-GIN, which converts generated biochemical descriptions into metabolite graphs for patient-level prediction using a graph isomorphism network. Across four backbone families, MetaboLLM outperformed corresponding base and medically adapted models on metabolomics knowledge, relational, and description tasks, and transferred to an external public benchmark. MetaboLLM-GIN achieved the highest AUC for stress hyperglycemia prediction after coronary artery bypass grafting (0.8616) and postmenopausal hormone-regimen classification (0.8123), outperforming conventional models, alternative graph constructions, and graphs generated from unadapted or non-retrieval LLM configurations. Model interpretation further produced biologically meaningful findings in both applications. These results show that domain-specialized language models can organize heterogeneous biochemical knowledge into predictive and interpretable metabolite graph representations.

One-dimensional nuclear magnetic resonance (NMR) spectroscopy is essential for molecular structure elucidation in organic synthesis, drug discovery, natural product characterization, and metabolomics, yet its interpretation remains heavily dependent on expert knowledge and difficult to scale. Although machine learning has been applied to NMR spectrum prediction, library retrieval, and structure generation, these tasks have evolved in isolation using simulated data and incompatible spectral representations, limiting their utility under real experimental scenarios. Here we present NMRPeak, a unified cross-modal learning system that integrates these three tasks through experimentally grounded design. We curate approximately 1.8 million experimental and simulated spectra to construct the largest benchmark for NMR-based structure elucidation and systematically quantify the distribution shift between these domains. We introduce a chemically-aware adaptive tokenizer that dynamically balances discretization granularity to preserve spectral semantics while controlling vocabulary size, and an assignment-free peak-aware similarity metric that enables direct comparison between predicted and experimental spectra. Through a unified molecule-to-spectrum paradigm and synergistic coupling of prediction, retrieval, and generation modules, NMRPeak achieves transformative performance on experimental benchmarks: it overcomes the longstanding simulation-to-experiment gap in spectrum prediction while delivering over 95% top-1 accuracy in molecular retrieval and approximately 75% top-1 accuracy in stereochemistry-aware de novo structure generation. These capabilities establish a foundation for automated, high-throughput molecular structure elucidation in organic synthesis, drug discovery, and chemical biology.

Understanding the 3D structures of protein multimers is crucial, as they play a vital role in regulating various cellular processes. It has been empirically confirmed that the multimer structure prediction~(MSP) can be well handled in a step-wise assembly fashion using provided dimer structures and predicted protein-protein interactions~(PPIs). However, due to the biological gap in the formation of dimers and larger multimers, directly applying PPI prediction techniques can often cause a poor generalization to the MSP task. To address this challenge, we aim to extend the PPI knowledge to multimers of different scales~(i.e., chain numbers). Specifically, we propose \textsc{PromptMSP}, a pre-training and Prompt tuning framework for Multimer Structure Prediction. First, we tailor the source and target tasks for effective PPI knowledge learning and efficient inference, respectively. We design PPI-inspired prompt learning to narrow the gaps of two task formats and generalize the PPI knowledge to multimers of different scales. We provide a meta-learning strategy to learn a reliable initialization of the prompt model, enabling our prompting framework to effectively adapt to limited data for large-scale multimers. Empirically, we achieve both significant accuracy (RMSD and TM-Score) and efficiency improvements compared to advanced MSP models. The code, data and checkpoints are released at https://github.com/zqgao22/PromptMSP.

This paper reviews the AIM 2020 challenge on efficient single image super-resolution with focus on the proposed solutions and results. The challenge task was to super-resolve an input image with a magnification factor x4 based on a set of prior examples of low and corresponding high resolution images. The goal is to devise a network that reduces one or several aspects such as runtime, parameter count, FLOPs, activations, and memory consumption while at least maintaining PSNR of MSRResNet. The track had 150 registered participants, and 25 teams submitted the final results. They gauge the state-of-the-art in efficient single image super-resolution.

Learning to optimize has emerged as a powerful framework for various optimization and machine learning tasks. Current such "meta-optimizers" often learn in the space of continuous optimization algorithms that are point-based and uncertainty-unaware. To overcome the limitations, we propose a meta-optimizer that learns in the algorithmic space of both point-based and population-based optimization algorithms. The meta-optimizer targets at a meta-loss function consisting of both cumulative regret and entropy. Specifically, we learn and interpret the update formula through a population of LSTMs embedded with sample- and feature-level attentions. Meanwhile, we estimate the posterior directly over the global optimum and use an uncertainty measure to help guide the learning process. Empirical results over non-convex test functions and the protein-docking application demonstrate that this new meta-optimizer outperforms existing competitors.

The efficient exploration of chemical space to design molecules with intended properties enables the accelerated discovery of drugs, materials, and catalysts, and is one of the most important outstanding challenges in chemistry. Encouraged by the recent surge in computer power and artificial intelligence development, many algorithms have been developed to tackle this problem. However, despite the emergence of many new approaches in recent years, comparatively little progress has been made in developing realistic benchmarks that reflect the complexity of molecular design for real-world applications. In this work, we develop a set of practical benchmark tasks relying on physical simulation of molecular systems mimicking real-life molecular design problems for materials, drugs, and chemical reactions. Additionally, we demonstrate the utility and ease of use of our new benchmark set by demonstrating how to compare the performance of several well-established families of algorithms. Surprisingly, we find that model performance can strongly depend on the benchmark domain. We believe that our benchmark suite will help move the field towards more realistic molecular design benchmarks, and move the development of inverse molecular design algorithms closer to designing molecules that solve existing problems in both academia and industry alike.

We introduce MetaICL (Meta-training for In-Context Learning), a new meta-training framework for few-shot learning where a pretrained language model is tuned to do in-context learning on a large set of training tasks. This meta-training enables the model to more effectively learn a new task in context at test time, by simply conditioning on a few training examples with no parameter updates or task-specific templates. We experiment on a large, diverse collection of tasks consisting of 142 NLP datasets including classification, question answering, natural language inference, paraphrase detection and more, across seven different meta-training/target splits. MetaICL outperforms a range of baselines including in-context learning without meta-training and multi-task learning followed by zero-shot transfer. We find that the gains are particularly significant for target tasks that have domain shifts from the meta-training tasks, and that using a diverse set of the meta-training tasks is key to improvements. We also show that MetaICL approaches (and sometimes beats) the performance of models fully finetuned on the target task, and outperforms much bigger models with nearly 8x parameters. Finally, we show that MetaICL is complementary to human-written instructions, and the best performance can be achieved by combining both approaches.

This paper introduces M^{3}-20M, a large-scale Multi-Modal Molecular dataset that contains over 20 million molecules. Designed to support AI-driven drug design and discovery, M^{3}-20M is 71 times more in the number of molecules than the largest existing dataset, providing an unprecedented scale that can highly benefit training or fine-tuning large (language) models with superior performance for drug design and discovery. This dataset integrates one-dimensional SMILES, two-dimensional molecular graphs, three-dimensional molecular structures, physicochemical properties, and textual descriptions collected through web crawling and generated by using GPT-3.5, offering a comprehensive view of each molecule. To demonstrate the power of M^{3}-20M in drug design and discovery, we conduct extensive experiments on two key tasks: molecule generation and molecular property prediction, using large language models including GLM4, GPT-3.5, and GPT-4. Our experimental results show that M^{3}-20M can significantly boost model performance in both tasks. Specifically, it enables the models to generate more diverse and valid molecular structures and achieve higher property prediction accuracy than the existing single-modal datasets, which validates the value and potential of M^{3}-20M in supporting AI-driven drug design and discovery. The dataset is available at https://github.com/bz99bz/M-3.

We propose an algorithm for meta-learning that is model-agnostic, in the sense that it is compatible with any model trained with gradient descent and applicable to a variety of different learning problems, including classification, regression, and reinforcement learning. The goal of meta-learning is to train a model on a variety of learning tasks, such that it can solve new learning tasks using only a small number of training samples. In our approach, the parameters of the model are explicitly trained such that a small number of gradient steps with a small amount of training data from a new task will produce good generalization performance on that task. In effect, our method trains the model to be easy to fine-tune. We demonstrate that this approach leads to state-of-the-art performance on two few-shot image classification benchmarks, produces good results on few-shot regression, and accelerates fine-tuning for policy gradient reinforcement learning with neural network policies.

Reward-based alignment methods for large language models (LLMs) face two key limitations: vulnerability to reward hacking, where models exploit flaws in the reward signal; and reliance on brittle, labor-intensive prompt engineering when LLMs are used as reward models. We introduce Meta Policy Optimization (MPO), a framework that addresses these challenges by integrating a meta-reward model that dynamically refines the reward model's prompt throughout training. In MPO, the meta-reward model monitors the evolving training context and continuously adjusts the reward model's prompt to maintain high alignment, providing an adaptive reward signal that resists exploitation by the policy. This meta-learning approach promotes a more stable policy optimization, and greatly reduces the need for manual reward prompt design. It yields performance on par with or better than models guided by extensively hand-crafted reward prompts. Furthermore, we show that MPO maintains its effectiveness across diverse tasks, such as question answering and mathematical reasoning, without requiring specialized reward designs. Beyond standard RLAIF, MPO's meta-learning formulation is readily extensible to higher-level alignment frameworks. Overall, this method addresses theoretical and practical challenges in reward-based RL alignment for LLMs, paving the way for more robust and adaptable alignment strategies. The code and models will be publicly shared.

The ability to quickly and accurately compute properties from atomic simulations is critical for advancing a large number of applications in chemistry and materials science including drug discovery, energy storage, and semiconductor manufacturing. To address this need, Meta FAIR presents a family of Universal Models for Atoms (UMA), designed to push the frontier of speed, accuracy, and generalization. UMA models are trained on half a billion unique 3D atomic structures (the largest training runs to date) by compiling data across multiple chemical domains, e.g. molecules, materials, and catalysts. We develop empirical scaling laws to help understand how to increase model capacity alongside dataset size to achieve the best accuracy. The UMA small and medium models utilize a novel architectural design we refer to as mixture of linear experts that enables increasing model capacity without sacrificing speed. For example, UMA-medium has 1.4B parameters but only ~50M active parameters per atomic structure. We evaluate UMA models on a diverse set of applications across multiple domains and find that, remarkably, a single model without any fine-tuning can perform similarly or better than specialized models. We are releasing the UMA code, weights, and associated data to accelerate computational workflows and enable the community to continue to build increasingly capable AI models.

We present a vector-based method to balance chemical reactions. The algorithm builds candidates in a deterministic way, removes duplicates, and always prints coefficients in the lowest whole-number form. For redox cases, electrons and protons/hydroxide are treated explicitly, so both mass and charge are balanced. We also outline the basic principles of the vector formulation of stoichiometry, interpreting reactions as integer vectors in composition space, this geometric view supports compact visualizations of reagent-product interactions and helps surface distinct reaction families. The method enumerates valid balances for arbitrary user-specified species lists without special-case balancing rules or symbolic tricks, and it provides a clean foundation for developing new algorithmic variants (e.g., alternative objectives or constraints). On representative examples (neutralization, double displacement, decomposition, classical redox, small multicomponent sets) and a negative control, the method produced correct integer balances. When multiple balances exist, we report a canonical one - minimizing the total coefficient sum with a simple tie-breaker - without claiming global optimality beyond the solutions the search enumerates. The procedure applies per reaction and extends to reaction networks via consistent per-reaction application. We do not report runtimes, broader benchmarking and code/data release are planned.

Project Greenhouse represents our exploration of a simple thesis: We believe that it is possible to build fully open and sovereign models for agentic search with only modest computational resources. As a first milestone, we describe how to build a competitive pointwise decoder-only reranker using a simple two-step recipe comprising pre-training from scratch followed by supervised fine-tuning, starting only from commonly available datasets. Contrary to the dominant approach in the literature, we do not rely on existing open-weight backbones from third parties, and thus we are fully in control of model training, from end to end. We were able to accomplish the bulk of our experiments using no more than a handful of GPUs. This report articulates the importance and benefits of our approach, and we share artifacts that enable transparent, independent reproduction of all aspects of model training. Beyond data, code, and configurations that capture our efforts, we also release checkpoints for our family of Gaggle models, demonstrating the feasibility of our approach and providing a first step toward validating our broader thesis.

Despite recent advancements, most computational methods for molecule optimization are constrained to single- or double-property optimization tasks and suffer from poor scalability and generalizability to novel optimization tasks. Meanwhile, Large Language Models (LLMs) demonstrate remarkable out-of-domain generalizability to novel tasks. To demonstrate LLMs' potential for molecule optimization, we introduce MoMUInstruct, the first high-quality instruction-tuning dataset specifically focused on complex multi-property molecule optimization tasks. Leveraging MoMUInstruct, we develop GeLLM^3Os, a series of instruction-tuned LLMs for molecule optimization. Extensive evaluations across 5 in-domain and 5 out-of-domain tasks demonstrate that GeLLM^3Os consistently outperform state-of-the-art baselines. GeLLM^3Os also exhibit outstanding zero-shot generalization to unseen tasks, significantly outperforming powerful closed-source LLMs. Such strong generalizability demonstrates the tremendous potential of GeLLM^3Os as foundational models for molecule optimization, thereby tackling novel optimization tasks without resource-intensive retraining. MoMUInstruct, models, and code are accessible through https://github.com/ninglab/GeLLMO.

An identification is found between meta-learning and the problem of determining the ground state of a randomly generated Hamiltonian drawn from a known ensemble. A model-agnostic meta-learning approach is proposed to solve the associated learning problem and a preliminary experimental study of random Max-Cut problems indicates that the resulting Meta Variational Monte Carlo accelerates training and improves convergence.

General-purpose large language models (LLMs) that rely on in-context learning do not reliably deliver the scientific understanding and performance required for drug discovery tasks. Simply increasing model size or introducing reasoning tokens does not yield significant performance gains. To address this gap, we introduce the MMAI Gym for Science, a one-stop shop molecular data formats and modalities as well as task-specific reasoning, training, and benchmarking recipes designed to teach foundation models the 'language of molecules' in order to solve practical drug discovery problems. We use MMAI Gym to train an efficient Liquid Foundation Model (LFM) for these applications, demonstrating that smaller, purpose-trained foundation models can outperform substantially larger general-purpose or specialist models on molecular benchmarks. Across essential drug discovery tasks - including molecular optimization, ADMET property prediction, retrosynthesis, drug-target activity prediction, and functional group reasoning - the resulting model achieves near specialist-level performance and, in the majority of settings, surpasses larger models, while remaining more efficient and broadly applicable in the domain.

Single-step retrosynthesis is a central component of computer-aided synthesis planning, yet its intrinsically one-to-many nature is poorly captured by single-answer evaluation and benchmarking protocols. To address this, we introduce Top-K prompting as a robust training and inference paradigm to better capture diverse, plausible reaction predictions. We compile CREED-CCV-2+USPTO-XL, an ultra-large-scale dataset of ~45.6 million verified reactions to train the C3LM (Chemistry Constraint-Consistent Language Model). By integrating fine-tuning with ChemCensor-based and novelty-oriented rewards, our model achieves state-of-the-art performance on the OOD URSA-expert-2026 benchmark. Further analysis of reaction uniqueness shows that LLMs and conventional models explore complementary reaction spaces, motivating ensemble-based retrosynthesis systems. Overall, our results establish Top-K, plausibility-aware training as a practical new direction for robust future LLM-based synthesis planning.

Competitive programming has become a key test of large language model reasoning, with international competitions such as IOI and ICPC representing its most challenging settings. We present an end-to-end specialization pipeline combining large-scale problem curation, synthetic reasoning traces, supervised fine-tuning (SFT), and reinforcement learning (RL). Using 22,000 curated problems, we train Nemotron-3-Nano-CC (30B-A3B) with SFT and RL and Nemotron-3-Ultra-CC (550B-A55B) with SFT alone. We further introduce GenCorrect, a feedback-driven test-time compute strategy that iteratively generates, evaluates, and refines diverse solutions. On IOI 2025, Nano-CC improves from 130 points to 291 after post-training and to 468 with GenCorrect, exceeding the gold threshold of 438.3 while Ultra-CC reaches 502. Guided by these results, we develop a competition-specific Ultra-CC system and evaluate it prospectively during IOI 2026. Under the same time, internet-access, and submission constraints as human contestants, it scores 535.4 out of 600, exceeding both the gold threshold of 361.12 and the top human score of 498.27. To our knowledge, this is the first AI system to outscore the highest-scoring human contestant on an IOI problem set.

Molecular machine learning has been maturing rapidly over the last few years. Improved methods and the presence of larger datasets have enabled machine learning algorithms to make increasingly accurate predictions about molecular properties. However, algorithmic progress has been limited due to the lack of a standard benchmark to compare the efficacy of proposed methods; most new algorithms are benchmarked on different datasets making it challenging to gauge the quality of proposed methods. This work introduces MoleculeNet, a large scale benchmark for molecular machine learning. MoleculeNet curates multiple public datasets, establishes metrics for evaluation, and offers high quality open-source implementations of multiple previously proposed molecular featurization and learning algorithms (released as part of the DeepChem open source library). MoleculeNet benchmarks demonstrate that learnable representations are powerful tools for molecular machine learning and broadly offer the best performance. However, this result comes with caveats. Learnable representations still struggle to deal with complex tasks under data scarcity and highly imbalanced classification. For quantum mechanical and biophysical datasets, the use of physics-aware featurizations can be more important than choice of particular learning algorithm.

Machine learning (ML) offers a powerful path toward discovering sustainable polymer materials, but progress has been limited by the lack of large, high-quality, and openly accessible polymer datasets. The Open Polymer Challenge (OPC) addresses this gap by releasing the first community-developed benchmark for polymer informatics, featuring a dataset with 10K polymers and 5 properties: thermal conductivity, radius of gyration, density, fractional free volume, and glass transition temperature. The challenge centers on multi-task polymer property prediction, a core step in virtual screening pipelines for materials discovery. Participants developed models under realistic constraints that include small data, label imbalance, and heterogeneous simulation sources, using techniques such as feature-based augmentation, transfer learning, self-supervised pretraining, and targeted ensemble strategies. The competition also revealed important lessons about data preparation, distribution shifts, and cross-group simulation consistency, informing best practices for future large-scale polymer datasets. The resulting models, analysis, and released data create a new foundation for molecular AI in polymer science and are expected to accelerate the development of sustainable and energy-efficient materials. Along with the competition, we release the test dataset at https://www.kaggle.com/datasets/alexliu99/neurips-open-polymer-prediction-2025-test-data. We also release the data generation pipeline at https://github.com/sobinalosious/ADEPT, which simulates more than 25 properties, including thermal conductivity, radius of gyration, and density.

Large language models are increasingly used as chemistry assistants, yet most chemistry benchmarks still score only final answers. This masks a critical failure mode: a model may output the correct molecule, product, or option while its reasoning violates chemical logic. Existing process-level evaluators are hard to scale because LLM judges and human step-level process annotation are costly, inconsistent, and vulnerable to hallucination. We introduce ChemCoTBench-V2, a rule-verifiable diagnostic benchmark for low-cost, auditable evaluation of structured, verifier-addressable chemical reasoning traces. It spans molecular understanding, molecule editing, molecular optimization, and reaction prediction, with 5,620 evaluation samples across 18 reporting tasks. Models must expose key intermediate steps in expert-designed templates, and those steps are checked with deterministic chemistry rules and, for closed-answer tasks, reference traces rather than another LLM judge. Open-ended molecular optimization is evaluated with oracle-verifiable state constraints rather than strict trace matching. The benchmark reports three separate signals: final-answer correctness, template adherence, and step-wise verifier correctness over expert-refined intermediate commitments. Experiments on frontier models reveal a persistent gap between final-answer success and structured-reasoning-state consistency: models often follow the requested format while failing chemical-step checks, or answer correctly with weak supporting reasoning. ChemCoTBench-V2 enables fine-grained model comparison and identifies the concrete step at which the trace first violates the verifier.

A persistent challenge in machine learning for scientific applications is jointly achieving prediction and understanding. Statistical models excel on structured data but operate as black boxes, while existing interpretability methods are largely inspective: they answer "which features matter?" but do not articulate how features interact or refine explanations iteratively alongside human understanding. Asking an LLM to predict the target directly forces it to search the entire output space; we instead anchor predictions with a base model and ask the LLM the narrower question of what that model is missing. We introduce Multi-Agent Residual In-Context Learning (MARICL), an agentic framework in which LLM agents analyze where a base-model fails, hypothesize missing structure from high-residual examples provided in context, and produce explicit correction terms refined through multi-turn textual gradient optimization. Across nine benchmarks spanning scientific, biomedical, socioeconomic, and synthetic settings, MARICL improves consistently over its base model on all datasets. To test whether these corrections reflect real structure or batch-specific noise, we freeze formulas learned on one experimental batch of the Cell-Free Protein dataset and apply them (with no retraining and no further LLM calls) to held-out batches. Within the same reagent protocol, the frozen formulas improve predictions in over 92% of cases; across a different protocol, they fail systematically. The success boundary aligns with the biochemistry, not the batch count; direct evidence of mechanistic generalization.

Recently, pre-trained foundation models have enabled significant advancements in multiple fields. In molecular machine learning, however, where datasets are often hand-curated, and hence typically small, the lack of datasets with labeled features, and codebases to manage those datasets, has hindered the development of foundation models. In this work, we present seven novel datasets categorized by size into three distinct categories: ToyMix, LargeMix and UltraLarge. These datasets push the boundaries in both the scale and the diversity of supervised labels for molecular learning. They cover nearly 100 million molecules and over 3000 sparsely defined tasks, totaling more than 13 billion individual labels of both quantum and biological nature. In comparison, our datasets contain 300 times more data points than the widely used OGB-LSC PCQM4Mv2 dataset, and 13 times more than the quantum-only QM1B dataset. In addition, to support the development of foundational models based on our proposed datasets, we present the Graphium graph machine learning library which simplifies the process of building and training molecular machine learning models for multi-task and multi-level molecular datasets. Finally, we present a range of baseline results as a starting point of multi-task and multi-level training on these datasets. Empirically, we observe that performance on low-resource biological datasets show improvement by also training on large amounts of quantum data. This indicates that there may be potential in multi-task and multi-level training of a foundation model and fine-tuning it to resource-constrained downstream tasks.

Text-guided molecular generation with LLMs often yields invalid SMILES. We argue that invalid drafts should be addressed through a shift from validity-oriented repair to identity-preserving molecular recovery: the objective is not only to restore chemical validity, but also to preserve target-relevant structural cues and recover the molecular identity implied by the description. This perspective reveals the limitations of existing correction strategies. Post-hoc repair can recover validity while distorting key structures, LLM-only correction can introduce unintended global drift, and generic agentic correction remains constrained by greedy single-candidate trajectories even when equipped with executable RDKit edit tools. To address these limitations, we propose AMREC, which couples molecule-aware mismatch tracking with expanded candidate exploration and trajectory-level selection. On invalid ChEBI-20 drafts from three backbone models, AMREC achieves the strongest overall recovery profile across structural, exact-match, and string-level metrics.

Data-free meta-learning (DFML) aims to enable efficient learning of new tasks by meta-learning from a collection of pre-trained models without access to the training data. Existing DFML work can only meta-learn from (i) white-box and (ii) small-scale pre-trained models (iii) with the same architecture, neglecting the more practical setting where the users only have inference access to the APIs with arbitrary model architectures and model scale inside. To solve this issue, we propose a Bi-level Data-free Meta Knowledge Distillation (BiDf-MKD) framework to transfer more general meta knowledge from a collection of black-box APIs to one single meta model. Specifically, by just querying APIs, we inverse each API to recover its training data via a zero-order gradient estimator and then perform meta-learning via a novel bi-level meta knowledge distillation structure, in which we design a boundary query set recovery technique to recover a more informative query set near the decision boundary. In addition, to encourage better generalization within the setting of limited API budgets, we propose task memory replay to diversify the underlying task distribution by covering more interpolated tasks. Extensive experiments in various real-world scenarios show the superior performance of our BiDf-MKD framework.

We introduce a new molecular dataset, named Alchemy, for developing machine learning models useful in chemistry and material science. As of June 20th 2019, the dataset comprises of 12 quantum mechanical properties of 119,487 organic molecules with up to 14 heavy atoms, sampled from the GDB MedChem database. The Alchemy dataset expands the volume and diversity of existing molecular datasets. Our extensive benchmarks of the state-of-the-art graph neural network models on Alchemy clearly manifest the usefulness of new data in validating and developing machine learning models for chemistry and material science. We further launch a contest to attract attentions from researchers in the related fields. More details can be found on the contest website https://alchemy.tencent.com. At the time of benchamrking experiment, we have generated 119,487 molecules in our Alchemy dataset. More molecular samples are generated since then. Hence, we provide a list of molecules used in the reported benchmarks.

Large language models (LLMs) have shown increasing capability in problem-solving and decision-making, largely based on the step-by-step chain-of-thought reasoning processes. However, it has been increasingly challenging to evaluate the reasoning capability of LLMs. Concretely, existing outcome-based benchmarks begin to saturate and become less sufficient to monitor the progress. To this end, we present a process-based benchmark MR-BEN that demands a meta reasoning skill, where LMs are asked to locate and analyse potential errors in automatically generated reasoning steps. MR-BEN is a comprehensive benchmark comprising 5,975 questions collected from human experts, covering various subjects such as physics, chemistry, logic, coding, and more. Through our designed metrics for assessing meta-reasoning on this benchmark, we identify interesting limitations and weaknesses of current LLMs (open-source and closed-source models). For example, open-source models are seemingly comparable to GPT-4 on outcome-based benchmarks, but they lag far behind on our benchmark, revealing the underlying reasoning capability gap between them. Our dataset and codes are available on https://randolph-zeng.github.io/Mr-Ben.github.io/.

Generative models for materials, especially inorganic crystals, hold potential to transform the theoretical prediction of novel compounds and structures. Advancement in this field depends critically on robust benchmarks and minimal, information-rich datasets that enable meaningful model evaluation. This paper critically examines common datasets and reported metrics for a crystal structure prediction taskx2014generating the most likely structures given the chemical composition of a material. We focus on three key issues: First, materials datasets should contain unique crystal structures; for example, we show that the widely-utilized carbon-24 dataset only contains approx40% unique structures. Second, materials datasets should not be split randomly if polymorphs of many different compositions are numerous, which we find to be the case for the perov-5 dataset. Third, benchmarks can mislead if used uncritically, e.g., reporting a match rate metric without considering the structural variety exhibited by identical building blocks. To address these oft-overlooked issues, we introduce several fixes. We provide revised versions of the carbon-24 dataset: one with duplicates removed, one deduplicated and split by number of atoms N, and two containing only identical structures but with different unit cells. We also propose a new split for the perov-5 dataset which ensures polymorphs are grouped within each split subset, setting a more sensible standard for benchmarking model performance. Finally, we present METRe and cRMSE, new model evaluation metrics that can correct existing issues with the match rate metric.

We introduce a machine learning model to predict atomization energies of a diverse set of organic molecules, based on nuclear charges and atomic positions only. The problem of solving the molecular Schrödinger equation is mapped onto a non-linear statistical regression problem of reduced complexity. Regression models are trained on and compared to atomization energies computed with hybrid density-functional theory. Cross-validation over more than seven thousand small organic molecules yields a mean absolute error of ~10 kcal/mol. Applicability is demonstrated for the prediction of molecular atomization potential energy curves.

Large Language Models (LLMs) with strong abilities in natural language processing tasks have emerged and have been rapidly applied in various kinds of areas such as science, finance and software engineering. However, the capability of LLMs to advance the field of chemistry remains unclear. In this paper,we establish a comprehensive benchmark containing 8 practical chemistry tasks, including 1) name prediction, 2) property prediction, 3) yield prediction, 4) reaction prediction, 5) retrosynthesis (prediction of reactants from products), 6)text-based molecule design, 7) molecule captioning, and 8) reagent selection. Our analysis draws on widely recognized datasets including BBBP, Tox21, PubChem, USPTO, and ChEBI, facilitating a broad exploration of the capacities of LLMs within the context of practical chemistry. Three GPT models (GPT-4, GPT-3.5,and Davinci-003) are evaluated for each chemistry task in zero-shot and few-shot in-context learning settings with carefully selected demonstration examples and specially crafted prompts. The key results of our investigation are 1) GPT-4 outperforms the other two models among the three evaluated; 2) GPT models exhibit less competitive performance in tasks demanding precise understanding of molecular SMILES representation, such as reaction prediction and retrosynthesis;3) GPT models demonstrate strong capabilities in text-related explanation tasks such as molecule captioning; and 4) GPT models exhibit comparable or better performance to classical machine learning models when applied to chemical problems that can be transformed into classification or ranking tasks, such as property prediction, and yield prediction.

This work proposes a procedure for designing algorithms for specific adaptive data collection tasks like active learning and pure-exploration multi-armed bandits. Unlike the design of traditional adaptive algorithms that rely on concentration of measure and careful analysis to justify the correctness and sample complexity of the procedure, our adaptive algorithm is learned via adversarial training over equivalence classes of problems derived from information theoretic lower bounds. In particular, a single adaptive learning algorithm is learned that competes with the best adaptive algorithm learned for each equivalence class. Our procedure takes as input just the available queries, set of hypotheses, loss function, and total query budget. This is in contrast to existing meta-learning work that learns an adaptive algorithm relative to an explicit, user-defined subset or prior distribution over problems which can be challenging to define and be mismatched to the instance encountered at test time. This work is particularly focused on the regime when the total query budget is very small, such as a few dozen, which is much smaller than those budgets typically considered by theoretically derived algorithms. We perform synthetic experiments to justify the stability and effectiveness of the training procedure, and then evaluate the method on tasks derived from real data including a noisy 20 Questions game and a joke recommendation task.

Supramolecular chemistry, which includes the study of non-covalent host-guest assemblies, has advanced various applications. However, designing host-guest systems remains time-consuming, requiring days of dry-lab verification per candidate pair. Although LLMs have emerged as a fast alternative with strong performance on molecular binding tasks, no benchmark currently systematically evaluates LLMs for host-guest reasoning across fundamental supramolecular chemistry tasks, e.g., binding affinity prediction. To this end, we collaborate with domain experts to release the first Supramolecular Benchmark, called SupraBench, to evaluate LLMs in chemistry reasoning. Specifically, we design four fundamental tasks, i.e., binding affinity prediction, top-binder selection, solvent identification, and host-guest description, plus an auxiliary vision-based task for molecular identification. We also release SupraPMC, a curated 16M-token corpus of Supramolecular chemistry articles distilled from Europe PMC, to support the adaptation to the supramolecular domain. We benchmark a broad range of open and proprietary LLMs and find that LLMs leave substantial headroom across all tasks. Domain adaptation pretraining over SupraPMC transfers cleanly to in-distribution regression but trades off against strict letter-format output. Moreover, the difficulty profile differs sharply across task families, revealing distinct failure modes that indicate specific gaps in current supramolecular chemistry reasoning. Our source codes and benchmark datasets are available at https://github.com/Tianyi-Billy-Ma/SupraBench.

Meta-reinforcement learning (meta-RL) is a promising framework for tackling challenging domains requiring efficient exploration. Existing meta-RL algorithms are characterized by low sample efficiency, and mostly focus on low-dimensional task distributions. In parallel, model-based RL methods have been successful in solving partially observable MDPs, of which meta-RL is a special case. In this work, we leverage this success and propose a new model-based approach to meta-RL, based on elements from existing state-of-the-art model-based and meta-RL methods. We demonstrate the effectiveness of our approach on common meta-RL benchmark domains, attaining greater return with better sample efficiency (up to 15times) while requiring very little hyperparameter tuning. In addition, we validate our approach on a slate of more challenging, higher-dimensional domains, taking a step towards real-world generalizing agents.

Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful tool for molecular structure analysis, and spectral artificial intelligence offers great potential for its rapid and automated interpretation. However, the scarcity of experimental NMR datasets has constrained deep learning in this domain to narrow, task-specific applications that lack broad generalization. Here, we introduce UltraNMR, a large-scale foundation model for NMR that leverages the intrinsic properties of NMR spectra to learn generalizable spectral representations. We collected 158 million paired simulated ^{1}H and ^{13}C NMR spectra to train UltraNMR, employing multiple domain-specific pre-training objectives. UltraNMR captures both intra-spectral and inter-spectral dependencies, enabling seamless simulation-to-real adaptation. We demonstrate that adapting UltraNMR to a range of molecular structure analysis tasks on experimental NMR spectra consistently yields state-of-the-art performance and clearly outperforms UltraNMR variants trained directly on downstream data without simulation pre-training. We also construct a large-scale NMR spectral vector library by encoding simulated NMR spectra using UltraNMR, covering 94 million unique molecules and enabling effective structure-aware retrieval. In real-world applications, UltraNMR facilitates the structural elucidation of two previously unknown natural products from Chinese herbal medicines recorded in the Chinese Pharmacopoeia. These results suggest that large-scale simulation pre-training can effectively bridge the simulation-to-real gap, enabling robust and generalizable molecular structure analysis of real-world NMR spectra.

Machine Learning Force Fields (MLFFs) are a promising alternative to expensive ab initio quantum mechanical molecular simulations. Given the diversity of chemical spaces that are of interest and the cost of generating new data, it is important to understand how MLFFs generalize beyond their training distributions. In order to characterize and better understand distribution shifts in MLFFs, we conduct diagnostic experiments on chemical datasets, revealing common shifts that pose significant challenges, even for large foundation models trained on extensive data. Based on these observations, we hypothesize that current supervised training methods inadequately regularize MLFFs, resulting in overfitting and learning poor representations of out-of-distribution systems. We then propose two new methods as initial steps for mitigating distribution shifts for MLFFs. Our methods focus on test-time refinement strategies that incur minimal computational cost and do not use expensive ab initio reference labels. The first strategy, based on spectral graph theory, modifies the edges of test graphs to align with graph structures seen during training. Our second strategy improves representations for out-of-distribution systems at test-time by taking gradient steps using an auxiliary objective, such as a cheap physical prior. Our test-time refinement strategies significantly reduce errors on out-of-distribution systems, suggesting that MLFFs are capable of and can move towards modeling diverse chemical spaces, but are not being effectively trained to do so. Our experiments establish clear benchmarks for evaluating the generalization capabilities of the next generation of MLFFs. Our code is available at https://tkreiman.github.io/projects/mlff_distribution_shifts/.

Writing competitive programming problems is exacting. Authors must: set constraints, input distributions, and edge cases that rule out shortcuts; target specific algorithms (e.g., max-flow, dynamic programming, data structures); and calibrate complexity beyond the reach of most competitors. We argue that this makes for an ideal test of general large language model capabilities and study whether they can do this reliably. We introduce AutoCode, which uses multiple rounds of validation to yield competition-grade problem statements and test cases. On held-out problems, AutoCode test suites approach 99% consistency with official judgments, a significant improvement over current state-of-the-art methods like HardTests, which achieve less than 81%. Furthermore, starting with a random seed problem, AutoCode can create novel variants with reference and brute-force solutions. By cross-verifying these generated solutions against test cases, we can further filter out malformed problems. Our system ensures high correctness, as verified by human experts. AutoCode successfully produces novel problems judged by Grandmaster-level (top 0.3%) competitive programmers to be of contest quality.

Lack of rigorous reproducibility and validation are major hurdles for scientific development across many fields. Materials science in particular encompasses a variety of experimental and theoretical approaches that require careful benchmarking. Leaderboard efforts have been developed previously to mitigate these issues. However, a comprehensive comparison and benchmarking on an integrated platform with multiple data modalities with both perfect and defect materials data is still lacking. This work introduces JARVIS-Leaderboard, an open-source and community-driven platform that facilitates benchmarking and enhances reproducibility. The platform allows users to set up benchmarks with custom tasks and enables contributions in the form of dataset, code, and meta-data submissions. We cover the following materials design categories: Artificial Intelligence (AI), Electronic Structure (ES), Force-fields (FF), Quantum Computation (QC) and Experiments (EXP). For AI, we cover several types of input data, including atomic structures, atomistic images, spectra, and text. For ES, we consider multiple ES approaches, software packages, pseudopotentials, materials, and properties, comparing results to experiment. For FF, we compare multiple approaches for material property predictions. For QC, we benchmark Hamiltonian simulations using various quantum algorithms and circuits. Finally, for experiments, we use the inter-laboratory approach to establish benchmarks. There are 1281 contributions to 274 benchmarks using 152 methods with more than 8 million data-points, and the leaderboard is continuously expanding. The JARVIS-Leaderboard is available at the website: https://pages.nist.gov/jarvis_leaderboard

Large Language Models (LLMs) are typically fine-tuned for reasoning tasks through a two-stage pipeline of Supervised Fine-Tuning (SFT) followed by Reinforcement Learning (RL), a process fraught with catastrophic forgetting and suboptimal trade-offs between imitation and exploration. Recent single-stage methods attempt to unify SFT and RL using heuristics, but lack a principled mechanism for dynamically balancing the two paradigms. In this paper, we reframe this challenge through the theoretical lens of implicit rewards, viewing SFT and RL not as distinct methods but as complementary reward signals. We introduce Adaptive Meta Fine-Tuning (AMFT), a novel single-stage algorithm that learns the optimal balance between SFT's implicit, path-level reward and RL's explicit, outcome-based reward. The core of AMFT is a meta-gradient adaptive weight controller that treats the SFT-RL balance as a learnable parameter, dynamically optimizing it to maximize long-term task performance. This forward-looking approach, regularized by policy entropy for stability, autonomously discovers an effective training curriculum. We conduct a comprehensive evaluation on challenging benchmarks spanning mathematical reasoning, abstract visual reasoning (General Points), and vision-language navigation (V-IRL). AMFT consistently establishes a new state-of-the-art and demonstrats superior generalization on out-of-distribution (OOD) tasks. Ablation studies and training dynamic analysis confirm that the meta-learning controller is crucial for AMFT's stability, sample efficiency, and performance, offering a more principled and effective paradigm for LLM alignment.Our codes are open-sourced via https://github.com/hlxtsyj/AMFT.

Deep learning has advanced mass spectrometry data interpretation, yet most models remain feature extractors rather than unified scoring frameworks. We present pUniFind, the first large-scale multimodal pre-trained model in proteomics that integrates end-to-end peptide-spectrum scoring with open, zero-shot de novo sequencing. Trained on over 100 million open search-derived spectra, pUniFind aligns spectral and peptide modalities via cross modality prediction and outperforms traditional engines across diverse datasets, particularly achieving a 42.6 percent increase in the number of identified peptides in immunopeptidomics. Supporting over 1,300 modifications, pUniFind identifies 60 percent more PSMs than existing de novo methods despite a 300-fold larger search space. A deep learning based quality control module further recovers 38.5 percent additional peptides including 1,891 mapped to the genome but absent from reference proteomes while preserving full fragment ion coverage. These results establish a unified, scalable deep learning framework for proteomic analysis, offering improved sensitivity, modification coverage, and interpretability.

Large language models (LLMs), especially Explicit Long Chain-of-Thought (CoT) reasoning models like DeepSeek-R1 and QWQ, have demonstrated powerful reasoning capabilities, achieving impressive performance in commonsense reasoning and mathematical inference. Despite their effectiveness, Long-CoT reasoning models are often criticized for their limited ability and low efficiency in knowledge-intensive domains such as molecule discovery. Success in this field requires a precise understanding of domain knowledge, including molecular structures and chemical principles, which is challenging due to the inherent complexity of molecular data and the scarcity of high-quality expert annotations. To bridge this gap, we introduce Mol-R1, a novel framework designed to improve explainability and reasoning performance of R1-like Explicit Long-CoT reasoning LLMs in text-based molecule generation. Our approach begins with a high-quality reasoning dataset curated through Prior Regulation via In-context Distillation (PRID), a dedicated distillation strategy to effectively generate paired reasoning traces guided by prior regulations. Building upon this, we introduce MoIA, Molecular Iterative Adaptation, a sophisticated training strategy that iteratively combines Supervised Fine-tuning (SFT) with Reinforced Policy Optimization (RPO), tailored to boost the reasoning performance of R1-like reasoning models for molecule discovery. Finally, we examine the performance of Mol-R1 in the text-based molecule reasoning generation task, showing superior performance against existing baselines.

This paper presents a comprehensive review of the NTIRE 2025 Challenge on Single-Image Efficient Super-Resolution (ESR). The challenge aimed to advance the development of deep models that optimize key computational metrics, i.e., runtime, parameters, and FLOPs, while achieving a PSNR of at least 26.90 dB on the DIV2K_LSDIR_valid dataset and 26.99 dB on the DIV2K_LSDIR_test dataset. A robust participation saw 244 registered entrants, with 43 teams submitting valid entries. This report meticulously analyzes these methods and results, emphasizing groundbreaking advancements in state-of-the-art single-image ESR techniques. The analysis highlights innovative approaches and establishes benchmarks for future research in the field.

Autoresearch offers a flexible paradigm for automating scientific tasks, in which an AI agent proposes, implements, evaluates, and refines candidate solutions against a quantitative objective. Here, we use composition-based materials-property prediction to test whether such agents can perform a task beyond model selection and hyperparameter optimization: the design of input descriptors. We introduce Automat, an autoresearch framework where a coding agent based on a large language model generates composition-only descriptors for chemical compounds and evaluates them using a random forest workflow. The agent is restricted to information derivable from chemical formulas and iteratively proposes, implements, and tests chemically motivated descriptor strategies. We apply Automat, with OpenAI Codex using GPT-5.5 as the coding agent, to the prediction of experimental band gaps in inorganic materials and Curie temperatures in ferromagnetic compounds. In both tasks, Automat improves over fractional-composition, Magpie, and combined fractional-composition/Magpie baselines, while producing descriptor families that are chemically interpretable. These results provide a demonstration that autoresearch agents can generate competitive, task-specific materials descriptors without manual feature engineering during the run. They also reveal current limitations, including descriptor redundancy, sensitivity to greedy feature expansion, and the need for explicit complexity control, descriptor pruning, and more sophisticated search strategies.

Chemical reasoning usually involves complex, multi-step processes that demand precise calculations, where even minor errors can lead to cascading failures. Furthermore, large language models (LLMs) encounter difficulties handling domain-specific formulas, executing reasoning steps accurately, and integrating code effectively when tackling chemical reasoning tasks. To address these challenges, we present ChemAgent, a novel framework designed to improve the performance of LLMs through a dynamic, self-updating library. This library is developed by decomposing chemical tasks into sub-tasks and compiling these sub-tasks into a structured collection that can be referenced for future queries. Then, when presented with a new problem, ChemAgent retrieves and refines pertinent information from the library, which we call memory, facilitating effective task decomposition and the generation of solutions. Our method designs three types of memory and a library-enhanced reasoning component, enabling LLMs to improve over time through experience. Experimental results on four chemical reasoning datasets from SciBench demonstrate that ChemAgent achieves performance gains of up to 46% (GPT-4), significantly outperforming existing methods. Our findings suggest substantial potential for future applications, including tasks such as drug discovery and materials science. Our code can be found at https://github.com/gersteinlab/chemagent

Text-to-optimization requires two separable capabilities: modeling -- choosing the right optimization structure -- and binding -- grounding every coefficient, index, and parameter in the concrete problem data. We study this via Text2Opt-Bench, a scalable benchmark of solver-verified optimization problems spanning 12 categories, from textbook linear programs to stochastic and multi-objective formulations with up to thousands of variables. Across 10+ models, we find that accuracy collapses as instance data grows, even when the formulation itself is simple. We call this the effective binding limit. We address this via a simple inference-time approach, BIND, which externalizes numeric data to structured files so the model binds data programmatically rather than transcribing from the prompt. BIND improves GPT-5-Nano from 59.1% to 82.4% accuracy, matching pass@5 (82.0%) at lower token cost than pass@1, and GPT-5 from 86.2% to 95.8%. Furthermore, we validate our hypothesis by finetuning a model exclusively on binding and show that it outperforms end-to-end SFT and RL across three structurally distinct optimization categories, with a 1.5B binding specialist alone matching a 7B end-to-end baseline.

Traditional methods for learning with the presence of noisy labels have successfully handled datasets with artificially injected noise but still fall short of adequately handling real-world noise. With the increasing use of meta-learning in the diverse fields of machine learning, researchers leveraged auxiliary small clean datasets to meta-correct the training labels. Nonetheless, existing meta-label correction approaches are not fully exploiting their potential. In this study, we propose an Enhanced Meta Label Correction approach abbreviated as EMLC for the learning with noisy labels (LNL) problem. We re-examine the meta-learning process and introduce faster and more accurate meta-gradient derivations. We propose a novel teacher architecture tailored explicitly to the LNL problem, equipped with novel training objectives. EMLC outperforms prior approaches and achieves state-of-the-art results in all standard benchmarks. Notably, EMLC enhances the previous art on the noisy real-world dataset Clothing1M by 1.52% while requiring times 0.5 the time per epoch and with much faster convergence of the meta-objective when compared to the baseline approach.

We study the use of amortized optimization to predict optimal transport (OT) maps from the input measures, which we call Meta OT. This helps repeatedly solve similar OT problems between different measures by leveraging the knowledge and information present from past problems to rapidly predict and solve new problems. Otherwise, standard methods ignore the knowledge of the past solutions and suboptimally re-solve each problem from scratch. We instantiate Meta OT models in discrete and continuous settings between grayscale images, spherical data, classification labels, and color palettes and use them to improve the computational time of standard OT solvers. Our source code is available at http://github.com/facebookresearch/meta-ot

Predictive models in biomedicine depend on structured assay data locked in the text, tables, and supplements of primary publications. This bottleneck is especially acute in targeted protein degradation (TPD), where each assay record must combine compound identity, degradation target, recruiter, assay context, and endpoint values reported across sections, tables, and supplementary files. Inconsistent compound identifiers and incomplete or implicit assay context further demand domain-specific logic that generic LLM pipelines do not provide. Existing molecular glue and PROTAC databases are manually curated and often lack the experimental context required for downstream modeling. We formulate TPD database extraction as a domain-specific curation task and present an expert-in-the-loop LLM workflow, evaluated through a triangular comparison among LLM predictions, standardized baseline records, and expert-annotated ground truth. A lightweight cross-validated prompt-refinement module adapts extraction instructions from scarce expert annotations. With only seven annotated molecular glue publications, the workflow achieved record-level F_1 = 0.98 and transferred to PROTACs by terminology substitution alone, maintaining record-level F_1 > 0.93. Applied at scale, it expanded molecular glue and PROTAC databases by 81% and 92% records, respectively, with 92% and 82.5% of newly recovered records validated as correct upon expert review. The workflow also recovered kinetic and assay-context information essential for cross-study potency comparison and condition-aware degradation modeling. We release the workflow, prompts, evaluation code, and extracted datasets as resources for TPD data curation and AI-assisted scientific curation more broadly.

Small-molecule identification from tandem mass spectrometry (MS/MS) remains a bottleneck in untargeted settings where spectral libraries are incomplete. While deep learning offers a solution, current approaches typically fall into two extremes: explicit generative models that construct molecular graphs atom-by-atom, or joint contrastive models that learn cross-modal subspaces from scratch. We introduce SpecBridge, a novel implicit alignment framework that treats structure identification as a geometric alignment problem. SpecBridge fine-tunes a self-supervised spectral encoder (DreaMS) to project directly into the latent space of a frozen molecular foundation model (ChemBERTa), and then performs retrieval by cosine similarity to a fixed bank of precomputed molecular embeddings. Across MassSpecGym, Spectraverse, and MSnLib benchmarks, SpecBridge improves top-1 retrieval accuracy by roughly 20-25% relative to strong neural baselines, while keeping the number of trainable parameters small. These results suggest that aligning to frozen foundation models is a practical, stable alternative to designing new architectures from scratch. The code for SpecBridge is released at https://github.com/HassounLab/SpecBridge.

Large Language Models (LLMs) present an intriguing avenue for exploration in the field of formal theorem proving. Nevertheless, their full potential, particularly concerning the mitigation of hallucinations and refinement through prover error messages, remains an area that has yet to be thoroughly investigated. To enhance the effectiveness of LLMs in the field, we introduce the Lyra, a new framework that employs two distinct correction mechanisms: Tool Correction (TC) and Conjecture Correction (CC). To implement Tool Correction in the post-processing of formal proofs, we leverage prior knowledge to utilize predefined prover tools (e.g., Sledgehammer) for guiding the replacement of incorrect tools. Tool Correction significantly contributes to mitigating hallucinations, thereby improving the overall accuracy of the proof. In addition, we introduce Conjecture Correction, an error feedback mechanism designed to interact with prover to refine formal proof conjectures with prover error messages. Compared to the previous refinement framework, the proposed Conjecture Correction refines generation with instruction but does not collect paired (generation, error & refinement) prompts. Our method has achieved state-of-the-art (SOTA) performance on both miniF2F validation (48.0% -> 55.3%) and test (45.5% -> 51.2%). We also present 3 IMO problems solved by Lyra. We believe Tool Correction (post-process for hallucination mitigation) and Conjecture Correction (subgoal adjustment from interaction with environment) could provide a promising avenue for future research in this field.

Elucidating molecular structures from spectra is a foundational problem in chemical and materials characterization, yet remains challenging due to spectral ambiguity and the vast molecular space. Although recent diffusion-based generators show strong promise for spectra-conditioned elucidation, existing methods struggle to learn robust spectra-structure relationships from limited paired data when relying solely on global spectral representation. Moreover, the repeated full sampling inference strategy incurs substantial computation overhead. To address these limitations, we propose MAST, a Motif-Augmented diffusion framework with Search Tree, for joint 2D-3D spectroscopic molecular structure elucidation. MAST introduces explicit, interpretable motif priors as intermediate evidences throughout denoising, reducing conditional ambiguity and facilitating spectra-conditioned optimization. We further cast diffusion sampling as reward-guided tree search to prioritize high-reward denoising trajectories, yielding a compact set of spectra-consistent candidates under limited budgets. On the QM9S multi-spectra benchmark, MAST achieves 94.89\% exact recovery and improves 3D fidelity, while preserving high chemical validity and stability. Code is available at https://github.com/Jia040223/MAST.

Large Language Models (LLMs) have shown growing potential in molecular sciences, but they often produce chemically inaccurate descriptions and struggle to recognize or justify potential errors. This raises important concerns about their robustness and reliability in scientific applications. To support more rigorous evaluation of LLMs in chemical reasoning, we present the MolErr2Fix benchmark, designed to assess LLMs on error detection and correction in molecular descriptions. Unlike existing benchmarks focused on molecule-to-text generation or property prediction, MolErr2Fix emphasizes fine-grained chemical understanding. It tasks LLMs with identifying, localizing, explaining, and revising potential structural and semantic errors in molecular descriptions. Specifically, MolErr2Fix consists of 1,193 fine-grained annotated error instances. Each instance contains quadruple annotations, i.e,. (error type, span location, the explanation, and the correction). These tasks are intended to reflect the types of reasoning and verification required in real-world chemical communication. Evaluations of current state-of-the-art LLMs reveal notable performance gaps, underscoring the need for more robust chemical reasoning capabilities. MolErr2Fix provides a focused benchmark for evaluating such capabilities and aims to support progress toward more reliable and chemically informed language models. All annotations and an accompanying evaluation API will be publicly released to facilitate future research.

Motivation: The development of novel compounds targeting proteins of interest is one of the most important tasks in the pharmaceutical industry. Deep generative models have been applied to targeted molecular design and have shown promising results. Recently, target-specific molecule generation has been viewed as a translation between the protein language and the chemical language. However, such a model is limited by the availability of interacting protein-ligand pairs. On the other hand, large amounts of unlabeled protein sequences and chemical compounds are available and have been used to train language models that learn useful representations. In this study, we propose exploiting pretrained biochemical language models to initialize (i.e. warm start) targeted molecule generation models. We investigate two warm start strategies: (i) a one-stage strategy where the initialized model is trained on targeted molecule generation (ii) a two-stage strategy containing a pre-finetuning on molecular generation followed by target specific training. We also compare two decoding strategies to generate compounds: beam search and sampling. Results: The results show that the warm-started models perform better than a baseline model trained from scratch. The two proposed warm-start strategies achieve similar results to each other with respect to widely used metrics from benchmarks. However, docking evaluation of the generated compounds for a number of novel proteins suggests that the one-stage strategy generalizes better than the two-stage strategy. Additionally, we observe that beam search outperforms sampling in both docking evaluation and benchmark metrics for assessing compound quality. Availability and implementation: The source code is available at https://github.com/boun-tabi/biochemical-lms-for-drug-design and the materials are archived in Zenodo at https://doi.org/10.5281/zenodo.6832145

Data-driven molecular discovery leverages artificial intelligence/machine learning (AI/ML) and generative modeling to filter and design novel molecules. Discovering novel molecules requires accurate out-of-distribution (OOD) predictions, but ML models struggle to generalize OOD. Currently, no systematic benchmarks exist for molecular OOD prediction tasks. We present BOOM, benchmarks for out-of-distribution molecular property predictions: a chemically-informed benchmark for OOD performance on common molecular property prediction tasks. We evaluate over 150 model-task combinations to benchmark deep learning models on OOD performance. Overall, we find that no existing model achieves strong generalization across all tasks: even the top-performing model exhibited an average OOD error 3x higher than in-distribution. Current chemical foundation models do not show strong OOD extrapolation, while models with high inductive bias can perform well on OOD tasks with simple, specific properties. We perform extensive ablation experiments, highlighting how data generation, pre-training, hyperparameter optimization, model architecture, and molecular representation impact OOD performance. Developing models with strong OOD generalization is a new frontier challenge in chemical ML. This open-source benchmark is available at https://github.com/FLASK-LLNL/BOOM

Tandem mass spectrometry has played a pivotal role in advancing proteomics, enabling the high-throughput analysis of protein composition in biological tissues. Many deep learning methods have been developed for de novo peptide sequencing task, i.e., predicting the peptide sequence for the observed mass spectrum. However, two key challenges seriously hinder the further advancement of this important task. Firstly, since there is no consensus for the evaluation datasets, the empirical results in different research papers are often not comparable, leading to unfair comparison. Secondly, the current methods are usually limited to amino acid-level or peptide-level precision and recall metrics. In this work, we present the first unified benchmark NovoBench for de novo peptide sequencing, which comprises diverse mass spectrum data, integrated models, and comprehensive evaluation metrics. Recent impressive methods, including DeepNovo, PointNovo, Casanovo, InstaNovo, AdaNovo and pi-HelixNovo are integrated into our framework. In addition to amino acid-level and peptide-level precision and recall, we evaluate the models' performance in terms of identifying post-tranlational modifications (PTMs), efficiency and robustness to peptide length, noise peaks and missing fragment ratio, which are important influencing factors while seldom be considered. Leveraging this benchmark, we conduct a large-scale study of current methods, report many insightful findings that open up new possibilities for future development.

Recent advances in Text-to-Image (T2I) generative models, such as Imagen, Stable Diffusion, and FLUX, have led to remarkable improvements in visual quality. However, their performance is fundamentally limited by the quality of training data. Web-crawled and synthetic image datasets often contain low-quality or redundant samples, which lead to degraded visual fidelity, unstable training, and inefficient computation. Hence, effective data selection is crucial for improving data efficiency. Existing approaches rely on costly manual curation or heuristic scoring based on single-dimensional features in Text-to-Image data filtering. Although meta-learning based method has been explored in LLM, there is no adaptation for image modalities. To this end, we propose **Alchemist**, a meta-gradient-based framework to select a suitable subset from large-scale text-image data pairs. Our approach automatically learns to assess the influence of each sample by iteratively optimizing the model from a data-centric perspective. Alchemist consists of two key stages: data rating and data pruning. We train a lightweight rater to estimate each sample's influence based on gradient information, enhanced with multi-granularity perception. We then use the Shift-Gsampling strategy to select informative subsets for efficient model training. Alchemist is the first automatic, scalable, meta-gradient-based data selection framework for Text-to-Image model training. Experiments on both synthetic and web-crawled datasets demonstrate that Alchemist consistently improves visual quality and downstream performance. Training on an Alchemist-selected 50% of the data can outperform training on the full dataset.

Molecule discovery serves as a cornerstone in numerous scientific domains, fueling the development of new materials and innovative drug designs. Recent developments of in-silico molecule discovery have highlighted the promising results of cross-modal techniques, which bridge molecular structures with their descriptive annotations. However, these cross-modal methods frequently encounter the issue of data scarcity, hampering their performance and application. In this paper, we address the low-resource challenge by utilizing artificially-real data generated by Large Language Models (LLMs). We first introduce a retrieval-based prompting strategy to construct high-quality pseudo data, then explore the optimal method to effectively leverage this pseudo data. Experiments show that using pseudo data for domain adaptation outperforms all existing methods, while also requiring a smaller model scale, reduced data size and lower training cost, highlighting its efficiency. Furthermore, our method shows a sustained improvement as the volume of pseudo data increases, revealing the great potential of pseudo data in advancing low-resource cross-modal molecule discovery.

Large pretrained models such as GPT-3 have had tremendous impact on modern natural language processing by leveraging self-supervised learning to learn salient representations that can be used to readily finetune on a wide variety of downstream tasks. We investigate the possibility of transferring such advances to molecular machine learning by building a chemical foundation model, ChemBERTa-2, using the language of SMILES. While labeled data for molecular prediction tasks is typically scarce, libraries of SMILES strings are readily available. In this work, we build upon ChemBERTa by optimizing the pretraining process. We compare multi-task and self-supervised pretraining by varying hyperparameters and pretraining dataset size, up to 77M compounds from PubChem. To our knowledge, the 77M set constitutes one of the largest datasets used for molecular pretraining to date. We find that with these pretraining improvements, we are competitive with existing state-of-the-art architectures on the MoleculeNet benchmark suite. We analyze the degree to which improvements in pretraining translate to improvement on downstream tasks.

Molecular function is largely determined by structure. Accurately aligning molecular structure with natural language is therefore essential for enabling large language models (LLMs) to reason about downstream chemical tasks. However, the substantial cost of human annotation makes it infeasible to construct large-scale, high-quality datasets of structure-grounded descriptions. In this work, we propose a fully automated annotation framework for generating precise molecular structure descriptions at scale. Our approach builds upon and extends a rule-based chemical nomenclature parser to interpret IUPAC names and construct enriched, structured XML metadata that explicitly encodes molecular structure. This metadata is then used to guide LLMs in producing accurate natural-language descriptions. Using this framework, we curate a large-scale dataset of approximately 163k molecule-description pairs. A rigorous validation protocol combining LLM-based and expert human evaluation on a subset of 2,000 molecules demonstrates a high description precision of 98.6%. The resulting dataset provides a reliable foundation for future molecule-language alignment, and the proposed annotation method is readily extensible to larger datasets and broader chemical tasks that rely on structural descriptions.

Constrained synthesizability is an unaddressed challenge in generative molecular design. In particular, designing molecules satisfying multi-parameter optimization objectives, while simultaneously being synthesizable and enforcing the presence of specific commercial building blocks in the synthesis. This is practically important for molecule re-purposing, sustainability, and efficiency. In this work, we propose a novel reward function called TANimoto Group Overlap (TANGO), which uses chemistry principles to transform a sparse reward function into a dense and learnable reward function -- crucial for reinforcement learning. TANGO can augment general-purpose molecular generative models to directly optimize for constrained synthesizability while simultaneously optimizing for other properties relevant to drug discovery using reinforcement learning. Our framework is general and addresses starting-material, intermediate, and divergent synthesis constraints. Contrary to most existing works in the field, we show that incentivizing a general-purpose (without any inductive biases) model is a productive approach to navigating challenging optimization scenarios. We demonstrate this by showing that the trained models explicitly learn a desirable distribution. Our framework is the first generative approach to tackle constrained synthesizability.

AI systems are being deployed on high-stakes, domain-specific workflows that demand correctness not just in the final output, but at every intermediate step. One such workflow is estimating a product carbon footprint (PCF), the greenhouse-gas emissions attributable to a physical product. AI agents are increasingly being used to generate PCFs, but existing evaluations score either total emissions (hiding error sources and cancelling mistakes) or sub-tasks in isolation (missing compositional interactions). We introduce PCFBench, the first benchmark to carve PCF modeling into independently-evaluable tasks that require decomposition, retrieval, ontology matching, and numerical extraction. It comprises 614 expert-labelled items across six tasks. Together they probe reasoning under under-specification, conflicting context, and numerical constraints. Across eight frontier LLMs from four providers, no single model dominates. Although the strongest models estimate total product emissions within 2 times of declared totals on 77% of products, this rate drops to 37-58% when the PCF is generated step by step, with only 45-75% obeying mass conservation. These failures undermine the transparency practitioners need to compare products and drive decarbonization. We release the dataset and evaluation harness to support targeted progress.

We propose the AIMO Interpretability Challenge, a competition on distinguishing robust from spurious reasoning in frontier mathematical language models based on the models' internal mechanisms. The challenge is motivated by a central limitation of standard reasoning benchmarks: strong final-answer accuracy does not reveal whether a model relies on stable reasoning mechanisms or exploits brittle reasoning shortcuts. Building on AI Mathematical Olympiad (AIMO) problems and submissions, together with resources from the Fields Model Initiative, the competition will provide (1) newly-published olympiad-level math reasoning problems and their symbolic representations, allowing generation of novel functional variants, (2) access to frontier reasoning models, and (3) assessments of models' adversarial robustness on these problems. Participants will use these resources, along with our computing infrastructure support, to develop methods for identifying which models solve problems robustly. Our competition will also create a new, open robustness benchmark and baseline systems, aiming to provide a lasting foundation for standard benchmarking in mathematical reasoning and interpretability. Scientifically, the competition connects interpretability and generalization research around a central question in AI research: can we determine if, and to what extent, the decision-making of frontier AI models is generalizable and thus, reliable?

Iterative methods are ubiquitous in large-scale scientific computing applications, and a number of approaches based on meta-learning have been recently proposed to accelerate them. However, a systematic study of these approaches and how they differ from meta-learning is lacking. In this paper, we propose a framework to analyze such learning-based acceleration approaches, where one can immediately identify a departure from classical meta-learning. We show that this departure may lead to arbitrary deterioration of model performance. Based on our analysis, we introduce a novel training method for learning-based acceleration of iterative methods. Furthermore, we theoretically prove that the proposed method improves upon the existing methods, and demonstrate its significant advantage and versatility through various numerical applications.

The focus of recent meta-learning research has been on the development of learning algorithms that can quickly adapt to test time tasks with limited data and low computational cost. Few-shot learning is widely used as one of the standard benchmarks in meta-learning. In this work, we show that a simple baseline: learning a supervised or self-supervised representation on the meta-training set, followed by training a linear classifier on top of this representation, outperforms state-of-the-art few-shot learning methods. An additional boost can be achieved through the use of self-distillation. This demonstrates that using a good learned embedding model can be more effective than sophisticated meta-learning algorithms. We believe that our findings motivate a rethinking of few-shot image classification benchmarks and the associated role of meta-learning algorithms. Code is available at: http://github.com/WangYueFt/rfs/.

Large Language Models(LLMs) have demonstrated remarkable performance across various domains, yet their capabilities in molecular reasoning remain insufficiently explored. Current approaches tend to rely heavily on general-purpose prompting, which lacks domain-specific molecular semantics, while those that use fine-tuning strategies often face challenges with interpretability and reasoning depth. To address these issues, we introduce MolReasoner, a two-stage framework designed to transition LLMs from memorization towards chemical reasoning. First, we propose Mol-SFT, which initializes the model's reasoning abilities via synthetic Chain-of-Thought(CoT) samples generated by GPT-4o and verified for chemical accuracy. Subsequently, Mol-RL applies reinforcement learning with specialized reward functions designed explicitly to align chemical structures with linguistic descriptions, thereby enhancing molecular reasoning capabilities. Our approach notably enhances interpretability, improving the model 's molecular understanding and enabling better generalization. Extensive experiments demonstrate that MolReasoner outperforms existing methods, and marking a significant shift from memorization-based outputs to robust chemical reasoning.

Retrieval-Augmented Generation (RAG) extends large language models (LLMs) beyond parametric knowledge, yet it is unclear when iterative retrieval-reasoning loops meaningfully outperform static RAG, particularly in scientific domains with multi-hop reasoning, sparse domain knowledge, and heterogeneous evidence. We provide the first controlled, mechanism-level diagnostic study of whether synchronized iterative retrieval and reasoning can surpass an idealized static upper bound (Gold Context) RAG. We benchmark eleven state-of-the-art LLMs under three regimes: (i) No Context, measuring reliance on parametric memory; (ii) Gold Context, where all oracle evidence is supplied at once; and (iii) Iterative RAG, a training-free controller that alternates retrieval, hypothesis refinement, and evidence-aware stopping. Using the chemistry-focused ChemKGMultiHopQA dataset, we isolate questions requiring genuine retrieval and analyze behavior with diagnostics spanning retrieval coverage gaps, anchor-carry drop, query quality, composition fidelity, and control calibration. Across models, Iterative RAG consistently outperforms Gold Context, with gains up to 25.6 percentage points, especially for non-reasoning fine-tuned models. Staged retrieval reduces late-hop failures, mitigates context overload, and enables dynamic correction of early hypothesis drift, but remaining failure modes include incomplete hop coverage, distractor latch trajectories, early stopping miscalibration, and high composition failure rates even with perfect retrieval. Overall, staged retrieval is often more influential than the mere presence of ideal evidence; we provide practical guidance for deploying and diagnosing RAG systems in specialized scientific settings and a foundation for more reliable, controllable iterative retrieval-reasoning frameworks.

Due to the unprecedented success of deep learning, it has become an integral component in several multimedia computing applications in todays world. Unfortunately, deep learning systems are not perfect and can fail, sometimes abruptly, without prior warning or explanation. While reducing the error rate of deep neural networks has been the primary focus of the multimedia community, the problem of predicting when a deep learning system is going to fail has received significantly less research attention. In this paper, we propose a simple yet effective framework, MetaErr, to address this under-explored problem in deep learning research. We train a meta-model whose goal is to predict whether a base deep neural network will succeed or fail in predicting a particular data sample, by observing the base models performance on a given learning task. The meta-model is completely agnostic of the architecture and training parameters of the base model. Such an error prediction system can be immensely useful in a variety of smart multimedia applications. Our empirical studies corroborate the promise and potential of our framework against competing baselines. We further demonstrate the usefulness of our framework to improve the performance of pseudo-labeling-based semi-supervised learning, and show that MetaErr outperforms several strong baselines on three benchmark computer vision datasets.

Commercial large language models (LLMs), like OpenAI's GPT-4 powering ChatGPT and Anthropic's Claude 3 Opus, have dominated natural language processing (NLP) benchmarks across different domains. New competing Open-Source alternatives like Mixtral 8x7B or Llama 3 have emerged and seem to be closing the gap while often offering higher throughput and being less costly to use. Open-Source LLMs can also be self-hosted, which makes them interesting for enterprise and clinical use cases where sensitive data should not be processed by third parties. We participated in the 12th BioASQ challenge, which is a retrieval augmented generation (RAG) setting, and explored the performance of current GPT models Claude 3 Opus, GPT-3.5-turbo and Mixtral 8x7b with in-context learning (zero-shot, few-shot) and QLoRa fine-tuning. We also explored how additional relevant knowledge from Wikipedia added to the context-window of the LLM might improve their performance. Mixtral 8x7b was competitive in the 10-shot setting, both with and without fine-tuning, but failed to produce usable results in the zero-shot setting. QLoRa fine-tuning and Wikipedia context did not lead to measurable performance gains. Our results indicate that the performance gap between commercial and open-source models in RAG setups exists mainly in the zero-shot setting and can be closed by simply collecting few-shot examples for domain-specific use cases. The code needed to rerun these experiments is available through GitHub.

Machine learning methods can be a valuable aid in the scientific process, but they need to face challenging settings where data come from inhomogeneous experimental conditions. Recent meta-learning methods have made significant progress in multi-task learning, but they rely on black-box neural networks, resulting in high computational costs and limited interpretability. Leveraging the structure of the learning problem, we argue that multi-environment generalization can be achieved using a simpler learning model, with an affine structure with respect to the learning task. Crucially, we prove that this architecture can identify the physical parameters of the system, enabling interpreable learning. We demonstrate the competitive generalization performance and the low computational cost of our method by comparing it to state-of-the-art algorithms on physical systems, ranging from toy models to complex, non-analytical systems. The interpretability of our method is illustrated with original applications to physical-parameter-induced adaptation and to adaptive control.

Developing accurate models for chemical reactors is often challenging due to the complexity of reaction kinetics and process dynamics. Traditional approaches require retraining models for each new system, limiting generalizability and efficiency. In this work, we take a step toward foundation models for chemical reactor modeling by introducing a neural network framework that generalizes across diverse reactor types and rapidly adapts to new chemical processes. Our approach leverages meta-learning to pretrain the model on a broad set of reactor dynamics, enabling efficient adaptation to unseen reactions with minimal data. To further enhance generalizability, we incorporate physics-informed fine-tuning, ensuring physically consistent adaptation to new reactor conditions. Our framework is evaluated across three integer-order fundamental reactor types - continuous stirred tank reactors, batch reactors, and plug flow reactors - demonstrating superior few-shot adaptation compared to conventional data-driven, physics-informed, and transfer learning approaches. By combining meta-learning with physics-informed adaptation, this work lays the foundation for a generalizable modeling framework, advancing the development of foundation models for chemical engineering applications. Source code is available at https://github.com/killingbear999/chemical-reactor-foundation-model.

We present miniF2F, a dataset of formal Olympiad-level mathematics problems statements intended to provide a unified cross-system benchmark for neural theorem proving. The miniF2F benchmark currently targets Metamath, Lean, Isabelle (partially) and HOL Light (partially) and consists of 488 problem statements drawn from the AIME, AMC, and the International Mathematical Olympiad (IMO), as well as material from high-school and undergraduate mathematics courses. We report baseline results using GPT-f, a neural theorem prover based on GPT-3 and provide an analysis of its performance. We intend for miniF2F to be a community-driven effort and hope that our benchmark will help spur advances in neural theorem proving.

Efficient equilibrium sampling of molecular conformations remains a core challenge in computational chemistry and statistical inference. Classical approaches such as molecular dynamics or Markov chain Monte Carlo inherently lack amortization; the computational cost of sampling must be paid in-full for each system of interest. The widespread success of generative models has inspired interest into overcoming this limitation through learning sampling algorithms. Despite performing on par with conventional methods when trained on a single system, learned samplers have so far demonstrated limited ability to transfer across systems. We prove that deep learning enables the design of scalable and transferable samplers by introducing Prose, a 280 million parameter all-atom transferable normalizing flow trained on a corpus of peptide molecular dynamics trajectories up to 8 residues in length. Prose draws zero-shot uncorrelated proposal samples for arbitrary peptide systems, achieving the previously intractable transferability across sequence length, whilst retaining the efficient likelihood evaluation of normalizing flows. Through extensive empirical evaluation we demonstrate the efficacy of Prose as a proposal for a variety of sampling algorithms, finding a simple importance sampling-based finetuning procedure to achieve superior performance to established methods such as sequential Monte Carlo on unseen tetrapeptides. We open-source the Prose codebase, model weights, and training dataset, to further stimulate research into amortized sampling methods and finetuning objectives.

Large language models (LLMs) have recently shown strong progress on scientific reasoning, yet two major bottlenecks remain. First, explicit retrieval fragments reasoning, imposing a hidden "tool tax" of extra tokens and steps. Second, multi-agent pipelines often dilute strong solutions by averaging across all candidates. We address these challenges with a unified framework that combines implicit retrieval and structured collaboration. At its foundation, a Monitor-based retrieval module operates at the token level, integrating external knowledge with minimal disruption to reasoning. On top of this substrate, Hierarchical Solution Refinement (HSR) iteratively designates each candidate as an anchor to be repaired by its peers, while Quality-Aware Iterative Reasoning (QAIR) adapts refinement to solution quality. On Humanity's Last Exam (HLE) Bio/Chem Gold, our framework achieves 48.3\% accuracy -- the highest reported to date, surpassing the strongest agent baseline by 13.4 points and leading frontier LLMs by up to 18.1 points, while simultaneously reducing token usage by 53.5\% and agent steps by 43.7\%. Results on SuperGPQA and TRQA confirm robustness across domains. Error analysis shows that reasoning failures and knowledge gaps co-occur in over 85\% of cases, while diversity analysis reveals a clear dichotomy: retrieval tasks benefit from solution variety, whereas reasoning tasks favor consensus. Together, these findings demonstrate how implicit augmentation and structured refinement overcome the inefficiencies of explicit tool use and uniform aggregation. Code is available at: https://github.com/tangxiangru/Eigen-1.

Recent advancements in large language models have opened new possibilities for generative molecular drug design. We present Chemlactica and Chemma, two language models fine-tuned on a novel corpus of 110M molecules with computed properties, totaling 40B tokens. These models demonstrate strong performance in generating molecules with specified properties and predicting new molecular characteristics from limited samples. We introduce a novel optimization algorithm that leverages our language models to optimize molecules for arbitrary properties given limited access to a black box oracle. Our approach combines ideas from genetic algorithms, rejection sampling, and prompt optimization. It achieves state-of-the-art performance on multiple molecular optimization benchmarks, including an 8% improvement on Practical Molecular Optimization compared to previous methods. We publicly release the training corpus, the language models and the optimization algorithm.

This paper provides a review of the NTIRE 2025 challenge on real-world face restoration, highlighting the proposed solutions and the resulting outcomes. The challenge focuses on generating natural, realistic outputs while maintaining identity consistency. Its goal is to advance state-of-the-art solutions for perceptual quality and realism, without imposing constraints on computational resources or training data. The track of the challenge evaluates performance using a weighted image quality assessment (IQA) score and employs the AdaFace model as an identity checker. The competition attracted 141 registrants, with 13 teams submitting valid models, and ultimately, 10 teams achieved a valid score in the final ranking. This collaborative effort advances the performance of real-world face restoration while offering an in-depth overview of the latest trends in the field.

Scientific discovery is an inherently creative and uncertain process, requiring reasoning beyond the recall of known knowledge. While many benchmarks have been proposed to evaluate large language model (LLM) performance on deep research tasks via multi-hop retrieval, their innovative reasoning abilities essential for true scientific discovery remain largely untested. We introduce a benchmark framework for evaluating model performance in scientific discovery and reasoning, building up from a raw problem to the classical null hypothesis test. In our framework, models initially receive only the topic and research question from a recent paper, with technical details progressively revealed. At each stage of information disclosure, the model is tasked with generating hypotheses that address the research question, which is compared with the conclusions from the original paper and evaluated via automated semantic similarity of constituent atomic claims. This progressive evaluation of semantic divergence from ground-truth conclusions enables assessment of a model's innovativeness (under minimal information) to grounded reasoning capabilities (under full experimental details), both critical for using LLMs for scientific discovery purposes. Our framework provides a foundation for systematically evaluating scientific reasoning and discovery capabilities in LLMs, crucial for advancing the development of next-generation AI scientist/co-scientist systems. Specifically, here we evaluate GPT-5, GPT-5.4, Gemini 2.5 pro, and Gemini 3.1 pro preview across 45 papers spanning bioactive materials, mechanical materials, and nanomaterials. We find that GPT-5.4 and Gemini 3.1 pro outperform their previous generation counterparts as expected, and GPT-5.4 in particular maintains 0.7 F1 score alignment with ground truth conclusions even under minimal context.

Large Language Models (LLMs) stand at the forefront of a number of Natural Language Processing (NLP) tasks. Despite the widespread adoption of LLMs in NLP, much of their potential in broader fields remains largely unexplored, and significant limitations persist in their design and implementation. Notably, LLMs struggle with structured data, such as graphs, and often falter when tasked with answering domain-specific questions requiring deep expertise, such as those in biology and chemistry. In this paper, we explore a fundamental question: Can LLMs effectively handle molecule prediction tasks? Rather than pursuing top-tier performance, our goal is to assess how LLMs can contribute to diverse molecule tasks. We identify several classification and regression prediction tasks across six standard molecule datasets. Subsequently, we carefully design a set of prompts to query LLMs on these tasks and compare their performance with existing Machine Learning (ML) models, which include text-based models and those specifically designed for analysing the geometric structure of molecules. Our investigation reveals several key insights: Firstly, LLMs generally lag behind ML models in achieving competitive performance on molecule tasks, particularly when compared to models adept at capturing the geometric structure of molecules, highlighting the constrained ability of LLMs to comprehend graph data. Secondly, LLMs show promise in enhancing the performance of ML models when used collaboratively. Lastly, we engage in a discourse regarding the challenges and promising avenues to harness LLMs for molecule prediction tasks. The code and models are available at https://github.com/zhiqiangzhongddu/LLMaMol.

Chemical reaction datasets such as USPTO suffer from substantial incompleteness, frequently missing byproducts, co-reactants, and stoichiometric coefficients. This limits their applicability and reliability in downstream applications. Here, we introduce CompleteRXN, a large-scale supervised benchmark for reaction completion under realistic missing-data conditions. We construct a dataset of aligned incomplete and atom-balanced reactions by mapping USPTO records to curated mechanistic reactions. We evaluate representative baselines, including a novel encoder-decoder reaction completion model with constrained decoding, the Constrained Reaction Balancer (CRB), and a recent algorithmic method, SynRBL. On our CompleteRXN benchmark, the CRB achieves high performance across splits of increasing difficulty, reaching 99.20% equivalence accuracy on the random split and 91.12% on the extreme out-of-distribution split. SynRBL produces many balanced and chemically plausible completions, but with lower accuracy on the benchmark test splits. Across all methods, performance degrades with increasing incompleteness. We observe a substantial drop when evaluating on reactions outside the benchmark (full uncurated USPTO), highlighting the gap between benchmark performance and practical robustness and motivating future work.

Recent advancements in language models have started a new era of superior information retrieval and content generation, with embedding models playing an important role in optimizing data representation efficiency and performance. While benchmarks like the Massive Text Embedding Benchmark (MTEB) have standardized the evaluation of general domain embedding models, a gap remains in specialized fields such as chemistry, which require tailored approaches due to domain-specific challenges. This paper introduces a novel benchmark, the Chemical Text Embedding Benchmark (ChemTEB), designed specifically for the chemical sciences. ChemTEB addresses the unique linguistic and semantic complexities of chemical literature and data, offering a comprehensive suite of tasks on chemical domain data. Through the evaluation of 34 open-source and proprietary models using this benchmark, we illuminate the strengths and weaknesses of current methodologies in processing and understanding chemical information. Our work aims to equip the research community with a standardized, domain-specific evaluation framework, promoting the development of more precise and efficient NLP models for chemistry-related applications. Furthermore, it provides insights into the performance of generic models in a domain-specific context. ChemTEB comes with open-source code and data, contributing further to its accessibility and utility.

Retrieval-Augmented Generation (RAG) enriches Large Language Models (LLMs) by combining their internal, parametric knowledge with external, non-parametric sources, with the goal of improving factual correctness and minimizing hallucinations. The LiveRAG 2025 challenge explores RAG solutions to maximize accuracy on DataMorgana's QA pairs, which are composed of single-hop and multi-hop questions. The challenge provides access to sparse OpenSearch and dense Pinecone indices of the Fineweb 10BT dataset. It restricts model use to LLMs with up to 10B parameters and final answer generation with Falcon-3-10B. A judge-LLM assesses the submitted answers along with human evaluators. By exploring distinct retriever combinations and RAG solutions under the challenge conditions, our final solution emerged using InstructRAG in combination with a Pinecone retriever and a BGE reranker. Our solution achieved a correctness score of 1.13 and a faithfulness score of 0.55, placing fourth in the SIGIR 2025 LiveRAG Challenge.

In the last few years, graph neural networks (GNNs) have become the standard toolkit for analyzing and learning from data on graphs. This emerging field has witnessed an extensive growth of promising techniques that have been applied with success to computer science, mathematics, biology, physics and chemistry. But for any successful field to become mainstream and reliable, benchmarks must be developed to quantify progress. This led us in March 2020 to release a benchmark framework that i) comprises of a diverse collection of mathematical and real-world graphs, ii) enables fair model comparison with the same parameter budget to identify key architectures, iii) has an open-source, easy-to-use and reproducible code infrastructure, and iv) is flexible for researchers to experiment with new theoretical ideas. As of December 2022, the GitHub repository has reached 2,000 stars and 380 forks, which demonstrates the utility of the proposed open-source framework through the wide usage by the GNN community. In this paper, we present an updated version of our benchmark with a concise presentation of the aforementioned framework characteristics, an additional medium-sized molecular dataset AQSOL, similar to the popular ZINC, but with a real-world measured chemical target, and discuss how this framework can be leveraged to explore new GNN designs and insights. As a proof of value of our benchmark, we study the case of graph positional encoding (PE) in GNNs, which was introduced with this benchmark and has since spurred interest of exploring more powerful PE for Transformers and GNNs in a robust experimental setting.