arXiv:2509.18140cs.LGcs.AI2025-09

用机器学习找糖尿病高风险人群,还能推导出新药靶点。

A Machine Learning Framework for Pathway-Driven Therapeutic Target Discovery in Metabolic Disorders

  • 结合逻辑回归与主成分分析预测糖尿病风险。
  • 78.43%准确率,无须基因数据也能定位关键通路。
  • 适合精准医疗研究者,可快速生成干预策略。

代谢疾病(尤其是2型糖尿病,T2DM)带来重大全球健康负担,尤其影响遗传易感群体如亚利桑那州南部的皮马印第安人。本研究提出一种新型机器学习框架,融合预测建模与基因无关的通路映射,识别高风险个体并发现潜在治疗靶点。基于皮马印第安人数据集,采用逻辑回归与t检验筛选关键预测因子,模型整体准确率达78.43%。为连接预测结果与生物学意义,构建通路映射策略,将预测因子关联至胰岛素信号、AMPK及PPAR等关键信号网络,实现机制解析而无需直接分子数据。在此基础上,提出双靶点GLP-1/GIP受体激动剂、AMPK激活剂、SIRT1调节剂及植物化学物等治疗策略,并通过通路富集分析验证其合理性。该框架推动精准医学发展,提供可解释、可扩展的早期筛查与靶向干预方案。主要贡献包括:(1) 开发结合逻辑回归与主成分分析(PCA)的T2DM风险预测框架;(2) 提出基因无关通路映射方法以生成机制洞见;(3) 针对高风险人群识别新型治疗策略。

原文摘要 · Abstract (English)

Metabolic disorders, particularly type 2 diabetes mellitus (T2DM), represent a significant global health burden, disproportionately impacting genetically predisposed populations such as the Pima Indians (a Native American tribe from south central Arizona). This study introduces a novel machine learning (ML) framework that integrates predictive modeling with gene-agnostic pathway mapping to identify high-risk individuals and uncover potential therapeutic targets. Using the Pima Indian dataset, logistic regression and t-tests were applied to identify key predictors of T2DM, yielding an overall model accuracy of 78.43%. To bridge predictive analytics with biological relevance, we developed a pathway mapping strategy that links identified predictors to critical signaling networks, including insulin signaling, AMPK, and PPAR pathways. This approach provides mechanistic insights without requiring direct molecular data. Building upon these connections, we propose therapeutic strategies such as dual GLP-1/GIP receptor agonists, AMPK activators, SIRT1 modulators, and phytochemical, further validated through pathway enrichment analyses. Overall, this framework advances precision medicine by offering interpretable and scalable solutions for early detection and targeted intervention in metabolic disorders. The key contributions of this work are: (1) development of an ML framework combining logistic regression and principal component analysis (PCA) for T2DM risk prediction; (2) introduction of a gene-agnostic pathway mapping approach to generate mechanistic insights; and (3) identification of novel therapeutic strategies tailored for high-risk populations.

糖尿病机器学习通路分析精准医疗

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