Modeling the transplacental transfer of small molecules using machine learning: a case study on per- and polyfluorinated substances (PFAS).
Modeling the transplacental transfer of small molecules using machine learning: a case study on per- and polyfluorinated substances (PFAS).
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利用机器学习模拟小分子经胎盘转移：全氟和多氟物质（PFAS）案例研究。
DOI：
10.1038/s41370-022-00481-2
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发表时间：
2022-11
影响因子：
4.5
通讯作者：
Woodruff, Tracey J.
中科院分区：
文献类型：
--
作者：
Abrahamsson, Dimitri;Siddharth, Adi;Robinson, Joshua F.;Soshilov, Anatoly;Elmore, Sarah;Cogliano, Vincent;Ng, Carla;Khan, Elaine;Ashton, Randolph;Chiu, Weihsueh A.;Fung, Jennifer;Zeise, Lauren;Woodruff, Tracey J.
尽管其数量众多且广泛使用，但对全氟烷基和多氟烷基物质（PFAS）可以穿过胎盘并暴露发育中的胎儿的程度知之甚少。我们研究的目的是开发一种计算方法，可用于评估小分子，特别是PFAS，可以穿过胎盘并分配到脐带血的程度。我们收集了260种化合物的脐带血和母血（RCM）浓度比的集中趋势的实验值，并使用化学信息学软件包Mordred计算了它们的理化描述符。我们开发并测试了一个人工神经网络（ANN），并使用编译的数据库来训练模型。然后，我们应用我们的最佳性能模型对PFAS化学品的大型数据集（n= 7，982）进行RCM预测。最后，我们使用计算的化学品的描述符，以确定哪些属性与RCM显着相关。我们确定了7855种化合物在我们模型的适用范围内，127种化合物在我们模型的适用范围之外。我们对PFAS的RCM的预测表明，3623种化合物的log RCM > 0，表明优选分配至脐带血。这些化合物的一些实例是双酚AF、2，2-双（4-氨基苯基）六氟丙烷和3-甲基丁酸壬基叔丁酯。这些观察结果具有重要的公共卫生意义，因为许多PFAS已被证明会干扰胎儿发育。
Despite their large numbers and widespread use, very little is known about the extent to which per- and polyfluoroalkyl substances (PFAS) can cross the placenta and expose the developing fetus. The aim of our study is to develop a computational approach that can be used to evaluate the of extend of which small molecules, and in particular PFAS, can cross to cross the placenta and partition to cord blood. We collected experimental values of the central tendency of concentration ratio between cord and maternal blood (RCM) for 260 chemical compounds and calculated their physicochemical descriptors using the cheminformatics package Mordred. We developed and tested an artificial neural network (ANN) and used the compiled database to train the model. We then applied our best performing model to make predictions of RCM for a large dataset of PFAS chemicals (n=7,982). We, finally, used the calculated descriptors of the chemicals to identify which properties correlated significantly with RCM. We determined that 7855 compounds were within the applicability domain and 127 compounds are outside the applicability domain of our model. Our predictions of RCM for PFAS suggested that 3623 compounds had a log RCM > 0 indicating preferable partitioning to cord blood. Some examples of these compounds were bisphenol AF, 2,2-bis(4-aminophenyl)hexafluoropropane and nonafluoro-tert-butyl 3-methylbutyrate. These observations have important public health implications as many PFAS have been shown to interfere with fetal development.
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影响因子：
8.6
作者：
Aniceto N;Freitas AA;Bender A;Ghafourian T
通讯作者：
Ghafourian T
产前接触全氟烷基物质和多氟烷基物质 (PFAS) 以及胎盘转移效率与血清蛋白-PFAS 复合物解离常数之间的关联
影响因子：
11.4
作者：
Gao, Ke;Zhuang, Taifeng;Jiang, Guibin
通讯作者：
Jiang, Guibin
影响因子：
5.6
作者：
Fourches D;Muratov E;Tropsha A
通讯作者：
Tropsha A
影响因子：
5.6
作者：
Fourches D;Muratov E;Tropsha A
通讯作者：
Tropsha A
影响因子：
10.4
作者：
Grandjean P;Heilmann C;Weihe P;Nielsen F;Mogensen UB;Budtz-Jørgensen E
通讯作者：
Budtz-Jørgensen E