arXiv:2606.06207cs.AIcs.LG2026-06

用无监督方法分析日本兽药不良反应,发现物种特异性毒性模式。

Unsupervised Pattern Analysis in Japanese Veterinary Toxicology: A Regulatory-Compliant Framework for Cross-Species Risk Assessment

论文配图:Unsupervised Pattern Analysis in Japanese Veterinary Toxicology: A Regulatory-Compliant Framework for Cross-Species Risk Assessment
图 1 · 摘自论文原文
  • 基于监管框架构建无监督分析模型,融合物种代谢差异与报告偏差。
  • 从4120例高质量报告中识别出三类显著毒性集群,准确率超80%。
  • 结果可解释性强,适合监管机构和兽药安全评估人员使用。

兽药警戒系统对监测药物不良反应(ADE)至关重要,但现有方法难以捕捉受本地生物和监管环境影响的区域特异性毒性模式。在日本,物种间代谢差异及农林水产省(MAFF)定义的报告实践进一步加剧了这一挑战。多数前期工作依赖预测模型,限制了机制可解释性。本研究提出一种整合监管要求的无监督框架,利用国家兽药检测实验室(NVAL)数据库进行模式发现。将ADE编码为器官系统对齐的表示,并校正物种特异性报告偏差,实现跨物种比较。采用基于相似性的聚类与降维方法识别潜在毒性结构。分析4,120例高置信度的ADE报告(共9,080个药物-ADE组合)后,发现三类显著物种集群(p < 0.01),包括宠物动物的肝毒性主导模式(0.42 ± 0.06)、反刍动物的肾毒性(0.39 ± 0.07)以及绵羊的皮肤敏感性(0.35 ± 0.07)。药物级聚类与药理类别匹配率达83%,余弦相似性优于其他度量(轮廓系数:0.48;聚类精确率:87%)。监管验证显示与既有分类高度一致。结果表明,符合监管要求的无监督分析可揭示生物学有意义、区域特异的毒性模式,为兽药安全评估提供可解释且可扩展的框架。

原文摘要 · Abstract (English)

Veterinary pharmacovigilance systems are essential for monitoring adverse drug events (ADEs), yet existing approaches often fail to capture region-specific toxicity patterns shaped by local biological and regulatory contexts. In Japan, these challenges are amplified by species-specific metabolic differences and reporting practices defined by the Ministry of Agriculture, Forestry, and Fisheries (MAFF). Most prior work relies on prediction-oriented models, limiting mechanistic interpretability. This study proposes a regulatory-integrated unsupervised framework for pattern discovery using the National Veterinary Assay Laboratory (NVAL) database. ADEs are encoded into organ system-aligned representations and adjusted for species-specific reporting biases, enabling cross-species comparison. Similarity-based clustering and dimensionality reduction are applied to identify latent toxicity structures. Analysis of 4,120 high-confidence ADE reports (9,080 drug-ADE combinations) identified three significant species clusters (p < 0.01), including hepatic-dominant patterns in companion animals (0.42 $\pm$ 0.06), renal toxicity in ruminants (0.39 $\pm$ 0.07), and dermatological sensitivity in sheep (0.35 $\pm$ 0.07). Drug-level clustering achieved 83% alignment with pharmacological classes, while cosine similarity outperformed alternative metrics (silhouette score: 0.48; cluster precision: 87%). Regulatory validation showed strong agreement with established classifications. These findings demonstrate that regulation-aligned unsupervised analysis can uncover biologically meaningful, region-specific toxicity patterns, providing an interpretable and scalable framework for veterinary drug safety assessment.

兽药安全无监督学习毒性分析数据合规

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