Bridging a diagnostic Kawasaki disease classifier from a microarray platform to a qRT-PCR assay.
Bridging a diagnostic Kawasaki disease classifier from a microarray platform to a qRT-PCR assay.
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DOI：
10.1038/s41390-022-02148-y
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发表时间：
2023-03
影响因子：
3.6
通讯作者：
Levin, Michael
中科院分区：
文献类型：
--
作者：
Kuiper, Rowan;Wright, Victoria J.;Habgood-Coote, Dominic;Shimizu, Chisato;Huigh, Daphne;Tremoulet, Adriana H.;van Keulen, Danielle;Hoggart, Clive J.;Rodriguez-Manzano, Jesus;Herberg, Jethro A.;Kaforou, Myrsini;Tempel, Dennie;Burns, Jane C.;Levin, Michael
川崎病（KD）是一种系统性血管炎，主要影响 5 岁以下儿童。高达 30% 的患者出现冠状动脉异常，通过早期治疗可以减少这种异常。川崎病的及时诊断具有挑战性，但随着最近发现的全血宿主反应分类器的发现，该分类器可以将川崎病患者与其他发热性疾病患者区分开来，这可能会变得更加简单。在这里，我们将这种基于微阵列的分类器与临床适用的定量逆转录聚合酶链反应 (qRT-PCR) 测定结合起来：川崎病基因表达谱 (KiDs-GEP) 分类器。我们设计并优化了 qRT-PCR 测定，并将其应用于先前用于分类器发现的样本子集，以重新加权原始分类器。 KiDs-GEP 分类器的性能与原始分类器相当，ROC 曲线下交叉验证面积分别为 0.964 [95% CI: 0.924–1.00] 和 0.992 [95% CI: 0.978–1.00]。两种分类器在各种疾病状况下都表现出相似的趋势，诊断为川崎病的个体与病毒感染的个体之间的区别最为明显。我们成功地将基于微阵列的分类器桥接到 KiDs-GEP 分类器中，这是一种更快速且更具成本效益的 qRT-PCR 检测方法，使 KD 诊断测试更接近医院临床实验室。川崎病需要进行诊断测试，但目前尚无法进行。我们描述了一步多重 qRT-PCR 测定的开发以及 Wright 等人之前描述的基于微阵列的宿主反应分类器的后续修改（即桥接）。桥接 KiDs-GEP 分类器在区分川崎病患者和发热对照方面表现良好。川崎病的宿主反应临床测试可适用于医院临床实验室。
Kawasaki disease (KD) is a systemic vasculitis that mainly affects children under 5 years of age. Up to 30% of patients develop coronary artery abnormalities, which are reduced with early treatment. Timely diagnosis of KD is challenging but may become more straightforward with the recent discovery of a whole-blood host response classifier that discriminates KD patients from patients with other febrile conditions. Here, we bridged this microarray-based classifier to a clinically applicable quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay: the Kawasaki Disease Gene Expression Profiling (KiDs-GEP) classifier. We designed and optimized a qRT-PCR assay and applied it to a subset of samples previously used for the classifier discovery to reweight the original classifier. The performance of the KiDs-GEP classifier was comparable to the original classifier with a cross-validated area under the ROC curve of 0.964 [95% CI: 0.924–1.00] vs 0.992 [95% CI: 0.978–1.00], respectively. Both classifiers demonstrated similar trends over various disease conditions, with the clearest distinction between individuals diagnosed with KD vs viral infections. We successfully bridged the microarray-based classifier into the KiDs-GEP classifier, a more rapid and more cost-efficient qRT-PCR assay, bringing a diagnostic test for KD closer to the hospital clinical laboratory. A diagnostic test is needed for Kawasaki disease and is currently not available. We describe the development of a One-Step multiplex qRT-PCR assay and the subsequent modification (i.e., bridging) of the microarray-based host response classifier previously described by Wright et al. The bridged KiDs-GEP classifier performs well in discriminating Kawasaki disease patients from febrile controls. This host response clinical test for Kawasaki disease can be adapted to the hospital clinical laboratory.
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影响因子：
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作者：
Hu, Bing;Li, Yun;Zhang, Yanqing
通讯作者：
Zhang, Yanqing
影响因子：
2.7
作者：
Etienne, W;Meyer, MH;Meyer, RA
通讯作者：
Meyer, RA
影响因子：
3.3
作者：
Berdej-Szczot, Elzbieta;Firek-Pedras, Malgorzata;Malecka-Tendera, Ewa
通讯作者：
Malecka-Tendera, Ewa
影响因子：
4.7
作者：
Duarte, Ricardo;Cisneros, Silvia;Fernandez, Gabriel;Castellon, Daniel;Cattani, Cesar;A Melo, Cintia;Apocada, Asier
通讯作者：
Apocada, Asier
影响因子：
2.6
作者：
Pilania RK;Jindal AK;Bhattarai D;Naganur SH;Singh S
通讯作者：
Singh S