Scaling-law mechanical marker for liver fibrosis diagnosis and drug screening through machine learning

Honghao Zhang, Jiu-Tao Hang, Zhuo Chang, Suihuai Yu, Hui Yang, Guang-Kui Xu
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Abstract

Studies of cell and tissue mechanics have shown that significant changes in cell and tissue mechanics during lesions and cancers are observed, which provides new mechanical markers for disease diagnosis based on machine learning. However, due to the lack of effective mechanic markers, only elastic modulus and iconographic features are currently used as markers, which greatly limits the application of cell and tissue mechanics in disease diagnosis. Here, we develop a liver pathological state classifier through a support vector machine method, based on high dimensional viscoelastic mechanical data. Accurate diagnosis and grading of hepatic fibrosis facilitates early detection and treatment and may provide an assessment tool for drug development. To this end, we used the viscoelastic parameters obtained from the analysis of creep responses of liver tissues by a self-similar hierarchical model and built a liver state classifier based on machine learning. Using this classifier, we implemented a fast classification of healthy, diseased, and mesenchymal stem cells (MSCs)-treated fibrotic live tissues, and our results showed that the classification accuracy of healthy and diseased livers can reach 0.99, and the classification accuracy of the three liver tissues mixed also reached 0.82. Finally, we provide screening methods for markers in the context of massive data as well as high-dimensional viscoelastic variables based on feature ablation for drug development and accurate grading of liver fibrosis. We propose a novel classifier that uses the dynamical mechanical variables as input markers, which can identify healthy, diseased, and post-treatment liver tissues.
通过机器学习诊断肝纤维化和筛选药物的尺度法机械标记物
细胞和组织力学研究表明,细胞和组织力学在病变和癌症期间会发生显著变化,这为基于机器学习的疾病诊断提供了新的力学标记。然而,由于缺乏有效的力学标记,目前只有弹性模量和图标特征被用作标记,这极大地限制了细胞和组织力学在疾病诊断中的应用。在此,我们基于高维粘弹性力学数据,通过支持向量机方法开发了肝脏病理状态分类器。肝纤维化的准确诊断和分级有助于早期发现和治疗,并可为药物开发提供评估工具。为此,我们利用自相似分层模型分析肝脏组织蠕变响应所获得的粘弹性参数,并基于机器学习建立了肝脏状态分类器。利用该分类器,我们对健康、病变和间充质干细胞(MSCs)处理过的纤维化活组织进行了快速分类,结果表明,健康和病变肝脏的分类准确率可达0.99,三种肝脏组织混合的分类准确率也达到了0.82。最后,我们提供了海量数据背景下的标志物筛选方法,以及基于特征消融的高维粘弹性变量,用于药物开发和肝纤维化的精确分级。我们提出了一种使用动态力学变量作为输入标记的新型分类器,它可以识别健康、患病和治疗后的肝脏组织。
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