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HIGH-THROUGHPUT IMAGING-BASED METHODS FOR PREDICTING CELL-TYPE-SPECIFIC TOXICITY OF XENOBIOTICS WITH DIVERSE CHEMICAL STRUCTURES

机译:基于高通量成像的化学结构多样的异种药物的细胞类型特异性毒性预测方法

摘要

The present invention provides methods for the prediction of in vivo cell-specific toxicity of a compound that combines high-throughput imaging of cultured cells, quantitative phenotypic profiling, and machine learning methods. More particularly, the invention provides a method for the prediction of in vivo renal proximal tubular-, bronchial-epithelial-, and alveolar-cell-specific toxicities of a soluble or particulate compound that comprises contacting cultured human kidney and pulmonary cells with the compound at a range of concentrations, then labeling the cells with DNA, γH2AX and actin markers and obtaining textural features, spatial correlation features, ratios of the markers, intensity features, cell count and morphology, estimating dose response curves and performing automatic classification of the compound using a random-forest algorithm.
机译:本发明提供了预测化合物的体内细胞特异性毒性的方法,该方法结合了培养细胞的高通量成像,定量表型分析和机器学习方法。更具体地,本发明提供了一种预测可溶性或颗粒状化合物的体内肾近端肾小管,支气管上皮细胞和肺泡细胞特异性毒性的方法,该方法包括使培养的人肾和肺细胞与该化合物接触。一定范围的浓度,然后用DNA,γH2AX和肌动蛋白标记物标记细胞,并获得质地特征,空间相关性特征,标记物的比率,强度特征,细胞计数和形态,估计剂量反应曲线并使用以下方法对化合物进行自动分类随机森林算法。

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