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

针对肺炎支原体肺炎的宿主特异性转录组反应诊断可指导儿科患者治疗

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作者: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

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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