arXiv:2608.28990cs.AIq-bio.MN2026-09

用AI发现人体组织间隐藏的蛋白质共丰度规律,助力疾病机制探索。

Agentic AI uncovers conserved cross-tissue protein co-abundance programs inaccessible to single-dataset analysis

论文配图:Agentic AI uncovers conserved cross-tissue protein co-abundance programs inaccessible to single-dataset analysis
图 1 · 摘自论文原文
  • 构建大尺度组织蛋白网络,通过多源数据融合识别保守共丰度簇。
  • 在41种组织的820对组合中发现1833个保守簇,骨髓最连通。
  • 揭示皮肤-骨髓等非显性关联,提出脑肠、肝-骨髓等新机制假说。

跨组织保存的蛋白质共丰度簇可揭示共享疾病机制和潜在治疗靶点,尤其当器官特异性疾病的蛋白在周边或易获取组织中汇聚时。但以往研究仅聚焦生物预选的组织对,未探索多数组合及隐含关系。本文提出一种基于大语言模型的智能体框架,用于大规模、证据驱动的组织特异性蛋白质共丰度网络比较。该框架构建组织网络,推导成对共识簇,并整合表达图谱、蛋白互作与复合物数据库、通路注释、疾病目录和文献证据。应用于41种人体组织和体液的全部820对组合,识别出1,833个跨406对组织的保守共丰度簇。结肠、滑膜液、血液、脑脊液和骨髓为最广泛连接组织,而簇最丰富的组合主要由骨髓主导。分析还揭示非显性关系:皮肤-骨髓对超越解剖邻近的骨-骨髓对;结肠-乳腺包含涉及细胞外基质重塑、脂质代谢和免疫调控的癌症相关簇。簇级分析生成进一步机制假说,包括脑-肠间外泌体/氧化还原/血清素辅因子轴,以及肝-骨髓应激反应轴,涉及白质病相关基因。结果提供了一个全局可比的保守蛋白共丰度图谱,是机制与治疗探索的假设生成资源。代码与数据见 https://github.com/Gry1005/AgenticAI-conserved-cross-tissue-protein-co-abundance。

原文摘要 · Abstract (English)

Protein co-abundance clusters preserved across tissues can reveal shared disease mechanisms and candidate therapeutic targets, particularly when proteins implicated in organ-confined diseases converge in peripheral or accessible tissues. However, previous cross-tissue studies have focused on biologically pre-selected tissue pairs, leaving most possible combinations and non-obvious relationships unexplored. We present an LLM-agent framework for large-scale, evidence-grounded comparison of tissue-specific protein co-abundance networks. The framework constructs tissue networks, derives pairwise consensus clusters, and integrates evidence from expression atlases, protein interaction and complex databases, pathway annotations, disease catalogues, and literature. Applied to all 820 pairwise combinations of 41 human tissues and fluids, it identified 1,833 conserved co-abundance clusters across 406 tissue pairs. Colon, synovial fluid, blood, cerebrospinal fluid, and bone marrow were the most broadly connected tissues, while the most cluster-rich pairs were dominated by bone marrow. The analysis also highlighted non-obvious relationships: skin-bone marrow exceeded the anatomically adjacent bone-bone marrow pair, while colon-breast contained cancer-relevant clusters involving extracellular-matrix remodeling, lipid metabolism, and immune modulation. Cluster-level analyses generated further mechanistic hypotheses, including a brain-gut extracellular-vesicle/redox/serotonin-cofactor axis and a liver-bone marrow stress-response axis involving genes linked to white matter disease. These results provide a global, comparable landscape of conserved protein co-abundance and a hypothesis-generating resource for mechanistic and therapeutic exploration. Code and data are available at https://github.com/Gry1005/AgenticAI-conserved-cross-tissue-protein-co-abundance.

蛋白质组学跨组织分析智能体疾病机制

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