A diagnostic host-specific transcriptome response for Mycoplasma pneumoniae pneumonia to guide pediatric patient treatment

IF 14.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2025-01-15 DOI:10.1038/s41467-025-55932-9
Sandra Viz-Lasheras, Alberto Gómez-Carballa, Xabier Bello, Irene Rivero-Calle, Ana Isabel Dacosta, Myrsini Kaforou, Dominic Habgood-Coote, Aubrey J. Cunnington, Marieke Emonts, Jethro A. Herberg, Victoria J. Wright, Enitan D. Carrol, Stephane C. Paulus, Werner Zenz, Daniela S. Kohlfürst, Nina Schweintzger, Michiel Van der Flier, Ronald de Groot, Luregn J. Schlapbach, Philipp Agyeman, Andrew J. Pollard, Colin Fink, Taco T. Kuijpers, Suzanne Anderson, Ulrich Von Both, Marko Pokorn, Dace Zavadska, María Tsolia, Henriëtte A. Moll, Clementien Vermont, Michael Levin, Federico Martinón-Torres, Antonio Salas
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Abstract

Mycoplasma pneumoniae causes atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to beta-lactams, which are the first-line treatment for typical pneumonia. Current diagnostic tests are time-consuming and have low specificity, leading clinicians to administer empirical antibiotics. Using a LASSO regression simulation approach and blood microarray data from 107 children with pneumonia (including 30 M. pneumoniae) we identify eight different transcriptomic signatures, ranging from 3-10 transcripts, that differentiate mycoplasma pneumonia from other bacterial/viral pneumonias with high accuracy (AUC: 0.84–0.95). Additionally, we demonstrate that existing signatures for broadly distinguishing viral/bacterial infections and viral/bacterial pneumonias are ineffective in distinguishing M. pneumoniae from viral pneumonia. The new signatures are successfully validated in an independent RNAseq cohort of children with pneumonia, demonstrating their robustness. The high sensibility of these signatures presents a valuable opportunity to guide the treatment and management of M. pneumoniae pneumonia patients.

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肺炎支原体会导致儿童和年轻人患上非典型肺炎。由于缺乏细胞壁,它对β-内酰胺类药物有抗药性,而β-内酰胺类药物是治疗典型肺炎的一线药物。目前的诊断测试耗时长且特异性低,导致临床医生不得不使用经验性抗生素。利用 LASSO 回归模拟方法和 107 名肺炎患儿(包括 30 名肺炎支原体感染者)的血液微阵列数据,我们确定了 8 种不同的转录组特征,从 3 到 10 个转录本不等,这些特征能准确区分支原体肺炎和其他细菌/病毒性肺炎(AUC:0.84-0.95)。此外,我们还证明了现有的用于广泛区分病毒/细菌感染和病毒/细菌性肺炎的特征在区分肺炎支原体和病毒性肺炎方面效果不佳。新特征在一个独立的肺炎患儿 RNAseq 队列中得到了成功验证,证明了它们的稳健性。这些特征的高度敏感性为指导肺炎双球菌肺炎患者的治疗和管理提供了宝贵的机会。
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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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