基于Copula的球孢子菌最低抑菌浓度谱重构与聚类
Copula-Based Reconstruction and Clustering of Coccidioides Minimum Inhibitory Concentration Profiles
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中文总结 AI 辅助
本研究基于Copula重构球孢子菌最低抑菌浓度谱，通过多种聚类方法分析发现跨药物依赖结构和目标类别观测数会影响聚类结论，模拟实验验证了高严重程度评分类别的恢复情况。
中文摘要 AI 辅助
球孢子菌病是一种真菌性肺部感染，流行于美国太平洋西北部、西南部部分地区，以及墨西哥、中美洲和南美洲。Thompson等人2017年的研究报告显示，许多被分析的球孢子菌分离株对氟康唑的最低抑菌浓度值升高，但对其他三唑类药物的最低抑菌浓度值相对较低。我们从已发表的药物特异性边际频率表中构建了172个合成联合最低抑菌浓度谱，使用高斯Copula将从各边际分布中采样的值跨药物配对，并使用k均值聚类、层次聚类和高斯混合模型检查潜在的跨药物模式。在选定的重构结果中，强制四聚类划分始终识别出卡泊芬净最低抑菌浓度的上尾部分。在评估的依赖场景中，间隙统计量在96%至100%的嵌套重构中支持单一聚类，未提供重构的多变量数据支持更广泛多聚类结构的证据。另一项模拟研究检验了从复合最低抑菌浓度评分的预先指定分位数定义的高严重程度评分类别的恢复情况，该研究涵盖20个患病率和测量噪声条件下的4000次重复实验，多类别调整兰德指数根据方法和患病率的不同从中等到高不等，而高严重程度评分类别的二元划分一致性在患病率为1%时接近零，尽管召回率仍接近1.0。因此，聚类结论取决于假设的跨药物依赖结构和目标类别中实际的观测数量。
英文摘要
Coccidioidomycosis is a fungal lung infection endemic to parts of the Pacific Northwest and southwestern United States, Mexico, Central America, and South America. A 2017 study by Thompson et al. reported that many analyzed Coccidioides isolates had elevated minimum inhibitory concentration values for fluconazole but comparatively low minimum inhibitory concentration values for other triazole drugs. We constructed 172 synthetic joint minimum inhibitory concentration profiles from the published drug-specific marginal frequency tables. Values sampled from each marginal distribution were paired across drugs using a Gaussian copula, and potential cross-drug patterns were examined using k-means clustering, hierarchical clustering, and Gaussian mixture models. On the selected reconstruction, a forced four-cluster partition consistently identified an upper caspofungin minimum-inhibitory-concentration tail. Across the evaluated dependence scenarios, the gap statistic favored a single cluster in 96% to 100% of nested reconstructions, providing no evidence that the reconstructed multivariate data supported a broader multicluster structure. A separate simulation study examined recovery of an upper-severity-score category defined from prespecified quantiles of a composite minimum-inhibitory-concentration score. The study included 4,000 replications across 20 prevalence and measurement-noise conditions. The multiclass adjusted Rand index ranged from moderate to high depending on the method and prevalence, whereas binary partition agreement for the upper-severity-score category approached zero at 1% prevalence even though recall remained near 1.0. Clustering conclusions therefore depended on the assumed cross-drug dependence structure and on the realized number of observations in the target category.
