arXiv:2603.20321q-bio.MNcs.AI2026-03被引 1

用知识图谱+大模型分析基因互作,解释更可信。

GIP-RAG: An Evidence-Grounded Retrieval-Augmented Framework for Interpretable Gene Interaction and Pathway Impact Analysis

  • 用多个数据库构建统一基因互作图谱,结合大模型进行逐步推理。
  • 能识别直接/间接调控关系,并生成有生物证据支持的解释。
  • 适合研究疾病机制和精准医疗的科研人员使用。

理解基因间的机制关系及其对生物通路的影响,对揭示疾病机制和推动精准医疗至关重要。尽管公共数据库中已有大量分子互作与通路数据,但整合异构知识源并在生物网络中实现可解释的多步推理仍具挑战。本文提出GIP-RAG(基于检索增强生成的基因互作预测),融合生物医学知识图谱与大语言模型(LLMs),用于推断与解释基因互作。该框架通过整合KEGG、WikiPathways、SIGNOR、Pathway Commons和PubChem的注释数据,构建统一的基因互作知识图谱。针对用户指定基因,查询驱动模块检索相关子图,并将其融入结构化提示,引导LLM进行分步推理,从而识别直接与间接调控关系,并生成基于生物证据的机制解释。此外,GIP-RAG包含通路级功能影响模块,可模拟基因扰动在信号网络中的传播,并评估潜在通路状态变化。在多种生物场景下的评估表明,该框架能生成一致、可解释且有证据支持的基因调控机制洞察。总体而言,GIP-RAG为知识图谱与检索增强型大模型的结合提供了一种通用且可解释的方法,适用于复杂分子系统的机制推理。

原文摘要 · Abstract (English)

Understanding mechanistic relationships among genes and their impacts on biological pathways is essential for elucidating disease mechanisms and advancing precision medicine. Despite the availability of extensive molecular interaction and pathway data in public databases, integrating heterogeneous knowledge sources and enabling interpretable multi-step reasoning across biological networks remain challenging. We present GIP-RAG (Gene Interaction Prediction through Retrieval-Augmented Generation), a computational framework that combines biomedical knowledge graphs with large language models (LLMs) to infer and interpret gene interactions. The framework constructs a unified gene interaction knowledge graph by integrating curated data from KEGG, WikiPathways, SIGNOR, Pathway Commons, and PubChem. Given user-specified genes, a query-driven module retrieves relevant subgraphs, which are incorporated into structured prompts to guide LLM-based stepwise reasoning. This enables identification of direct and indirect regulatory relationships and generation of mechanistic explanations supported by biological evidence. Beyond pairwise interactions, GIP-RAG includes a pathway-level functional impact module that simulates propagation of gene perturbations through signaling networks and evaluates potential pathway state changes. Evaluation across diverse biological scenarios demonstrates that the framework generates consistent, interpretable, and evidence-supported insights into gene regulatory mechanisms. Overall, GIP-RAG provides a general and interpretable approach for integrating knowledge graphs with retrieval-augmented LLMs to support mechanistic reasoning in complex molecular systems.

基因互作知识图谱大模型可解释性

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