构建首个癌症患者蛋白组学指令数据集,让大模型读懂个体肿瘤机制。
Patient-specific Biomolecular Instruction Tuning
- 基于40万条患者蛋白组数据,构建可指导临床解读的指令数据集
- 提出KRONOS框架,融合分子互作拓扑学习患者特异性图表示
- 在肿瘤分型、分期预测等任务中表现优异,助力精准医疗
蛋白质组学数据对理解疾病表型的致病机制至关重要。在癌症中,分子特征分析可通过识别驱动个体化肿瘤进展、治疗耐药和临床异质性的生物过程,实现精准医学。近年来,多模态大语言模型(LLMs)展现出整合与跨异构数据模态推理的强大能力。然而,针对患者特异性蛋白组学进行多模态语言建模仍面临两大挑战:(1)缺乏可支持从蛋白组数据进行临床解释的指令微调数据集;(2)缺少能捕捉分子数据丰富异质性的语言建模范式。本文提出CPTAC-PROTSTRUCT,首个用于肿瘤学分子理解的指令微调数据集,包含来自最大国家级蛋白质组学癌症研究(CPTAC)的40万余条个性化蛋白组谱数据生成的开放性样本。同时,我们提出KRONOS(基于结构化微调的肿瘤学患者组学网络知识表征),一种新颖的图-语言模型框架,利用分子互作拓扑结构与蛋白组数据联合学习患者特异性图表示,以增强临床推理能力。实验表明,KRONOS在多个基准临床任务中表现优异,包括分子分类、时间轨迹建模和肿瘤分期预测。该方法使大模型能够理解患者层面的致病机制,推动精准医学在更准确诊断、预后判断和治疗分层方面的应用。
原文摘要 · Abstract (English)
Proteomics data is essential to pathogenic understanding of a disease phenotype. In cancer, analysis of molecular signatures enables precision medicine through the identification of biological processes that drive individualized tumor progression, therapeutic resistance, and clinical heterogeneity. Recent advances in multimodal large language models (LLMs) have shown remarkable capacity to integrate and reason across heterogeneous data modalities. However, performing multi-modal language modeling for molecular understanding of patient-specific proteomics remains a significant challenge due to two barriers: (1) the lack of instruction-tuning datasets that enable clinical interpretation from proteomics data, and (2) the absence of language modeling architectures designed to capture the rich heterogeneity of molecular data. In this work, we introduce CPTAC-PROTSTRUCT, the first instruction tuning dataset for molecular understanding of oncology, comprising over 400k open-ended examples derived from individualized proteomic profiles curated from the largest national proteomics cancer study (CPTAC). Additionally, we propose KRONOS (Knowledge Representation of patient Omics Networks in Oncology via Structured tuning), a novel graph-LLM framework that leverages molecular interaction topology with proteomics to learn patient-specific graph representations for enhanced clinical reasoning. We show that KRONOS achieves competitive performance across benchmark clinical tasks, including molecular classification, temporal trajectory modeling, and tumor stage prediction from proteomics data. Ultimately, this approach empowers LLMs to understand patient-level pathogenesis, advancing precision medicine through more accurate diagnosis, prognosis, and treatment stratification.
Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。