用图增强语言模型,让癌症靶点发现更可解释。
GALAX: Graph-Augmented Language Model for Explainable Reinforcement-Guided Subgraph Reasoning in Precision Medicine
- 将图神经网络融入大模型,通过强化学习逐步生成疾病相关子图。
- 在多个癌细胞系上验证,能准确识别已知靶点并支持长文本-数值图推理。
- 适合生物医学研究者和精准医疗中的可解释性分析需求。
在精准医疗中,多组学定量特征、拓扑结构与文本生物知识对识别疾病关键信号通路和靶点至关重要。现有方法仅捕捉部分信息:数值组学忽略拓扑上下文,以文本为中心的LLM缺乏定量推理基础,纯图模型则忽视节点语义与LLM泛化能力,限制了机制可解释性。尽管过程奖励模型(PRMs)旨在引导大模型推理,但受限于不可靠的中间评估及奖励劫持风险,且计算成本高。为此,我们提出GALAX(Graph-Augmented LAnguage model with eXplainability),通过图过程奖励模型(GPRM)引导强化学习,将预训练图神经网络(GNN)融入大模型(LLM),以逐步生成疾病相关子图。该过程由大模型启动,经预训练GNN和基于模式的规则检查迭代评估,实现无需显式标签的过程级监督。作为应用,我们构建了Target-QA基准,整合CRISPR确认靶点、多组学数据与生物图谱,覆盖多种癌细胞系,支持GNN预训练以指导子图构建,并支撑文本-数值图(TNGs)的长上下文推理,为精准医疗中的可解释、强化引导子图推理提供可扩展且生物学可信的框架。
原文摘要 · Abstract (English)
In precision medicine, quantitative multi-omic features, topological context, and textual biological knowledge play vital roles in identifying disease-critical signaling pathways and targets. Existing pipelines capture only part of these-numerical omics ignore topological context, text-centric LLMs lack quantitative grounded reasoning, and graph-only models underuse node semantics and the generalization of LLMs-limiting mechanistic interpretability. Although Process Reward Models (PRMs) aim to guide reasoning in LLMs, they remain limited by unreliable intermediate evaluation, and vulnerability to reward hacking with computational cost. These gaps motivate integrating quantitative multi-omic signals, topological structure with node annotations, and literature-scale text via LLMs, using subgraph reasoning as the principle bridge linking numeric evidence, topological knowledge and language context. Therefore, we propose GALAX (Graph Augmented LAnguage model with eXplainability), an innovative framework that integrates pretrained Graph Neural Networks (GNNs) into Large Language Models (LLMs) via reinforcement learning guided by a Graph Process Reward Model (GPRM), which generates disease-relevant subgraphs in a step-wise manner initiated by an LLM and iteratively evaluated by a pretrained GNN and schema-based rule check, enabling process-level supervision without explicit labels. As an application, we also introduced Target-QA, a benchmark combining CRISPR-identified targets, multi-omic profiles, and biomedical graph knowledge across diverse cancer cell lines, which enables GNN pretraining for supervising step-wise graph construction and supports long-context reasoning over text-numeric graphs (TNGs), providing a scalable and biologically grounded framework for explainable, reinforcement-guided subgraph reasoning toward reliable and interpretable target discovery in precision medicine.
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