背景:国际指南在如何最好地诊断原发性纤毛运动障碍(PCD)方面存在分歧,尤其是因为许多测试依赖于模式识别。我们假设纤毛超微结构和运动异常的定量分布将通过软计算分析检测最常见的引起PCD的基因群。
方法:对212例PCD患者的透射电子显微镜和高速视频分析的存档数据进行了重新检查,以定量超微结构(10个参数)和功能性纤毛特征(4个搏动模式和2个频率参数)的分布。通过前两个主成分的盲聚类分析来评估超微结构和运动特征之间的相关性,从每位患者的超微结构变量中获得。将软计算应用于超微结构,通过回归模型预测纤毛搏动频率(CBF)和运动模式。另一个模型将患者分为五个最常见的PCD致病基因组,从它们的超微结构来看,CBF和节拍模式。
结果:患者被细分为6个与同源超微结构表型相似的簇,运动模式,和CBF,除了簇1和簇4,可归因于正常的超微结构。回归模型证实了从超微结构参数预测功能性纤毛特征的能力。遗传分类模型确定了大多数不同的基因组,从所有定量参数开始。
结论:将软计算方法应用于PCD诊断测试,通过从模式识别转向定量来优化其价值。该方法也可用于评估非典型PCD,和新的遗传异常的不清楚的疾病产生的潜力在未来。
BACKGROUND: International guidelines disagree on how best to diagnose primary ciliary dyskinesia (PCD), not least because many tests rely on pattern recognition. We hypothesized that quantitative distribution of ciliary ultrastructural and motion abnormalities would detect most frequent PCD-causing groups of genes by soft computing analysis.
METHODS: Archived data on transmission electron microscopy and high-speed video analysis from 212 PCD patients were re-examined to quantitate distribution of ultrastructural (10 parameters) and functional ciliary features (4 beat pattern and 2 frequency parameters). The correlation between ultrastructural and motion features was evaluated by blinded clustering analysis of the first two principal components, obtained from ultrastructural variables for each patient. Soft computing was applied to ultrastructure to predict ciliary beat frequency (CBF) and motion patterns by a regression model. Another model classified the patients into the five most frequent PCD-causing gene groups, from their ultrastructure, CBF and beat patterns.
RESULTS: The patients were subdivided into six clusters with similar values to homologous ultrastructural phenotype, motion patterns, and CBF, except for clusters 1 and 4, attributable to normal ultrastructure. The regression model confirmed the ability to predict functional ciliary features from ultrastructural parameters. The genetic classification model identified most of the different groups of genes, starting from all quantitative parameters.
CONCLUSIONS: Applying soft computing methodologies to PCD diagnostic tests optimizes their value by moving from pattern recognition to quantification. The approach may also be useful to evaluate atypical PCD, and novel genetic abnormalities of unclear disease-producing potential in the future.