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A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia

Lookup NU author(s): Professor Marieke Emonts-le ClercqORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).

Abstract

© 2025 The Author(s)Pneumonia stands as the primary cause of death among children under five, yet current diagnosis methods often result in inadequate or unnecessary treatments. Our research seeks to address this gap by identifying host transcriptomic biomarkers in the blood of children with definitive viral and bacterial pneumonia. We performed RNA sequencing on 192 prospectively collected whole blood samples, including 38 controls and 154 pneumonia cases, uncovering a 5-transcript signature (genes FAM20A, BAG3, TDRD9, MXRA7, and KLF14) that effectively distinguishes bacterial from viral pneumonia (area under the curve (AUC): 0.95 [0.88–1.00]). Initial validation using combined definitive and probable cases yielded an AUC of 0.87 [0.77–0.97], while full validation in a new prospective cohort of 32 patients achieved an AUC of 0.92 [0.83–1.00]. This robust signature holds significant potential to enhance diagnostics accuracy for pediatric pneumonia, reducing diagnostic delays and unnecessary treatments and potentially transforming clinical practice.

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Author(s): Viz-Lasheras S, Gomez-Carballa A, Pardo-Seco J, Bello X, Rivero-Calle I, Dacosta AI, Kaforou M, Habgood-Coote D, Cunnington AJ, Emonts M, Herberg JA, Wright VJ, Carrol ED, Paulus SC, Zenz W, Kohlfurst DS, Van der Flier M, de Groot R, Schlapbach LJ, Agyeman P, Pollard AJ, Fink C, Kuijpers TT, Anderson S, Calvo C, Martinez-Padilla MDC, Perez-Aragon A, Gomez-Sanchez E, Valencia-Ramos J, Gimenez-Sanchez F, Alonso-Quintela P, Moreno-Galarraga L, von Both U, Pokorn M, Zavadska D, Tsolia M, Vermont CL, Moll HA, Levin M, Martinon-Torres F, Salas A, DIAMONDS Consortium, GENDRES Consortium, EUCLIDS Consortium, PERFORM Consortium

Publication type: Article

Publication status: Published

Journal: iScience

Year: 2025

Volume: 28

Issue: 2

Online publication date: 21/02/2025

Acceptance date: 02/01/2025

Date deposited: 28/01/2025

ISSN (electronic): 2589-0042

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.isci.2025.111747

DOI: 10.1016/j.isci.2025.111747

Data Access Statement: Data and code availability • RNA-seq data supporting the findings of the present study are publicly available at Gene Expression Omnibus (GEO) under accession number GSE261482 and EBI ArrayExpress under accession number E-MTAB-11671,105 E-MTAB-12793,106 and E-MTAB-14564. Additional details are provided in Table S7. • Original R code has been deposited at GitHub (https://github.com/Sandraviz/Pneumonia_Transcriptomic-Analysis). • Any additional information required to analyze the data reported in this paper is available upon request.

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