Yuanhao Qu

Xinming Tu, Tianze Wang, Yingzhou et al.

As benchmarks grow in complexity, many apparent agent failures are not failures of the agent at all - they are failures of the benchmark itself: broken specifications, implicit assumptions, and rigid evaluation scripts that penalize valid alternative approaches. We propose employing frontier LLMs as systematic auditors of evaluation infrastructure, and realize this vision through BenchGuard, the first automated auditing framework for task-oriented, execution-based agent benchmarks. BenchGuard cross-verifies all benchmark artifacts via structured LLM protocols, optionally incorporating agent solutions or execution traces as additional diagnostic evidence. Deployed on two prominent scientific benchmarks, BenchGuard identified 12 author-confirmed issues in ScienceAgentBench - including fatal errors rendering tasks unsolvable - and exactly matched 83.3% of expert-identified issues on the BIXBench Verified-50 subset, catching defects that prior human review missed entirely. A full audit of 50 complex bioinformatics tasks costs under USD 15, making automated benchmark auditing a practical and valuable complement to human review. These findings point toward AI-assisted benchmark development, where frontier models serve not only as subjects of evaluation but as active participants in validating the evaluation infrastructure itself.

Zhangde Song, Jieyu Lu, Yuanqi Du et al.

Large language models (LLMs) are increasingly applied to scientific research, yet prevailing science benchmarks probe decontextualized knowledge and overlook the iterative reasoning, hypothesis generation, and observation interpretation that drive scientific discovery. We introduce a scenario-grounded benchmark that evaluates LLMs across biology, chemistry, materials, and physics, where domain experts define research projects of genuine interest and decompose them into modular research scenarios from which vetted questions are sampled. The framework assesses models at two levels: (i) question-level accuracy on scenario-tied items and (ii) project-level performance, where models must propose testable hypotheses, design simulations or experiments, and interpret results. Applying this two-phase scientific discovery evaluation (SDE) framework to state-of-the-art LLMs reveals a consistent performance gap relative to general science benchmarks, diminishing return of scaling up model sizes and reasoning, and systematic weaknesses shared across top-tier models from different providers. Large performance variation in research scenarios leads to changing choices of the best performing model on scientific discovery projects evaluated, suggesting all current LLMs are distant to general scientific "superintelligence". Nevertheless, LLMs already demonstrate promise in a great variety of scientific discovery projects, including cases where constituent scenario scores are low, highlighting the role of guided exploration and serendipity in discovery. This SDE framework offers a reproducible benchmark for discovery-relevant evaluation of LLMs and charts practical paths to advance their development toward scientific discovery.

Ming Yin, Yuanhao Qu, Ling Yang et al.

We investigate how to teach large language models (LLMs) to perform scientific reasoning by leveraging expert discussions as a learning signal. Focusing on the genomics domain, we develop an automated pipeline to extract trainable data and introduce Genome-Bench, a new benchmark constructed from over a decade of scientific forum discussions on genome engineering. Our pipeline transforms raw interactions into a reinforcement learning-friendly multiple-choice questions format, supported by 3000+ high-quality question-answer pairs spanning foundational biology, experimental troubleshooting, tool usage, and beyond. We fine-tune an LLM using RL with a rule-based reward signal derived from the synthetic MCQ dataset to enhance domain-specific reasoning. Our results show that reinforcement learning from scientific discussions improves model performance by over 15% compared to the base model on Genome-Bench, narrowing the gap between open-source LLMs and expert-level reasoning. To our knowledge, this is the first end-to-end pipeline for teaching LLMs to reason from scientific discussions, with promising potential for generalization across scientific domains beyond biology.

Yuanhao Qu, Kaixuan Huang, Ming Yin et al.

The introduction of genome engineering technology has transformed biomedical research, making it possible to make precise changes to genetic information. However, creating an efficient gene-editing system requires a deep understanding of CRISPR technology, and the complex experimental systems under investigation. While Large Language Models (LLMs) have shown promise in various tasks, they often lack specific knowledge and struggle to accurately solve biological design problems. In this work, we introduce CRISPR-GPT, an LLM agent augmented with domain knowledge and external tools to automate and enhance the design process of CRISPR-based gene-editing experiments. CRISPR-GPT leverages the reasoning ability of LLMs to facilitate the process of selecting CRISPR systems, designing guide RNAs, recommending cellular delivery methods, drafting protocols, and designing validation experiments to confirm editing outcomes. We showcase the potential of CRISPR-GPT for assisting non-expert researchers with gene-editing experiments from scratch and validate the agent's effectiveness in a real-world use case. Furthermore, we explore the ethical and regulatory considerations associated with automated gene-editing design, highlighting the need for responsible and transparent use of these tools. Our work aims to bridge the gap between beginner biological researchers and CRISPR genome engineering techniques, and demonstrate the potential of LLM agents in facilitating complex biological discovery tasks. The published version of this draft is available at https://www.nature.com/articles/s41551-025-01463-z.