Interleaved Tool-Call Reasoning for Protein Function Understanding

Fuente: arXiv
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Autores principales: Fan, Chuanliu, Ma, Zicheng, Meng, Huanran, Zhang, Aijia, Du, Wenjie, Zhang, Jun, Gao, Yi Qin, Cao, Ziqiang, Fu, Guohong
Formato: Preprint
Publicado: 2026
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author Fan, Chuanliu
Ma, Zicheng
Meng, Huanran
Zhang, Aijia
Du, Wenjie
Zhang, Jun
Gao, Yi Qin
Cao, Ziqiang
Fu, Guohong
author_facet Fan, Chuanliu
Ma, Zicheng
Meng, Huanran
Zhang, Aijia
Du, Wenjie
Zhang, Jun
Gao, Yi Qin
Cao, Ziqiang
Fu, Guohong
contents Recent advances in large language models (LLMs) have highlighted the effectiveness of chain-of-thought reasoning in symbolic domains such as mathematics and programming. However, our study shows that directly transferring such text-based reasoning paradigms to protein function understanding is ineffective: reinforcement learning mainly amplifies superficial keyword patterns while failing to introduce new biological knowledge, resulting in limited generalization. We argue that protein function prediction is a knowledge-intensive scientific task that fundamentally relies on external biological priors and computational tools rather than purely internal reasoning. To address this gap, we propose PFUA, a tool-augmented protein reasoning agent that unifies problem decomposition, tool invocation, and grounded answer generation. Instead of relying on long unconstrained reasoning traces, PFUA integrates domain-specific tools to produce verifiable intermediate evidence. Experiments on four benchmarks demonstrate that PFUA consistently outperforms text-only reasoning models with an average performance improvement of 103%.
format Preprint
id arxiv_https___arxiv_org_abs_2601_03604
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Interleaved Tool-Call Reasoning for Protein Function Understanding
Fan, Chuanliu
Ma, Zicheng
Meng, Huanran
Zhang, Aijia
Du, Wenjie
Zhang, Jun
Gao, Yi Qin
Cao, Ziqiang
Fu, Guohong
Artificial Intelligence
Recent advances in large language models (LLMs) have highlighted the effectiveness of chain-of-thought reasoning in symbolic domains such as mathematics and programming. However, our study shows that directly transferring such text-based reasoning paradigms to protein function understanding is ineffective: reinforcement learning mainly amplifies superficial keyword patterns while failing to introduce new biological knowledge, resulting in limited generalization. We argue that protein function prediction is a knowledge-intensive scientific task that fundamentally relies on external biological priors and computational tools rather than purely internal reasoning. To address this gap, we propose PFUA, a tool-augmented protein reasoning agent that unifies problem decomposition, tool invocation, and grounded answer generation. Instead of relying on long unconstrained reasoning traces, PFUA integrates domain-specific tools to produce verifiable intermediate evidence. Experiments on four benchmarks demonstrate that PFUA consistently outperforms text-only reasoning models with an average performance improvement of 103%.
title Interleaved Tool-Call Reasoning for Protein Function Understanding
topic Artificial Intelligence
url https://arxiv.org/abs/2601.03604