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

Summary: 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 a...

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Main Authors: Sandra Viz-Lasheras, Alberto Gómez-Carballa, Jacobo Pardo-Seco, 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, Michiel Van der Flier, Ronald de Groot, Luregn J. Schlapbach, Philipp Agyeman, Andrew J. Pollard, Colin Fink, Taco T. Kuijpers, Suzanne Anderson, Cristina Calvo, María del Carmen Martínez-Padilla, Ana Pérez-Aragón, Esteban Gómez-Sánchez, Juan Valencia-Ramos, Francisco Giménez-Sánchez, Paula Alonso-Quintela, Laura Moreno-Galarraga, Ulrich von Both, Marko Pokorn, Dace Zavadska, María Tsolia, Clementien L. Vermont, Henriëtte A. Moll, Michael Levin, Federico Martinón-Torres, Antonio Salas
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Language:English
Published: Elsevier 2025-02-01
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225000069
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author Sandra Viz-Lasheras
Alberto Gómez-Carballa
Jacobo Pardo-Seco
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
Michiel Van der Flier
Ronald de Groot
Luregn J. Schlapbach
Philipp Agyeman
Andrew J. Pollard
Colin Fink
Taco T. Kuijpers
Suzanne Anderson
Cristina Calvo
María del Carmen Martínez-Padilla
Ana Pérez-Aragón
Esteban Gómez-Sánchez
Juan Valencia-Ramos
Francisco Giménez-Sánchez
Paula Alonso-Quintela
Laura Moreno-Galarraga
Ulrich von Both
Marko Pokorn
Dace Zavadska
María Tsolia
Clementien L. Vermont
Henriëtte A. Moll
Michael Levin
Federico Martinón-Torres
Antonio Salas
author_facet Sandra Viz-Lasheras
Alberto Gómez-Carballa
Jacobo Pardo-Seco
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
Michiel Van der Flier
Ronald de Groot
Luregn J. Schlapbach
Philipp Agyeman
Andrew J. Pollard
Colin Fink
Taco T. Kuijpers
Suzanne Anderson
Cristina Calvo
María del Carmen Martínez-Padilla
Ana Pérez-Aragón
Esteban Gómez-Sánchez
Juan Valencia-Ramos
Francisco Giménez-Sánchez
Paula Alonso-Quintela
Laura Moreno-Galarraga
Ulrich von Both
Marko Pokorn
Dace Zavadska
María Tsolia
Clementien L. Vermont
Henriëtte A. Moll
Michael Levin
Federico Martinón-Torres
Antonio Salas
author_sort Sandra Viz-Lasheras
collection DOAJ
description Summary: 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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spelling doaj-art-34e8bfdac40344a181935441b7b82c4e2025-01-23T05:27:36ZengElsevieriScience2589-00422025-02-01282111747A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumoniaSandra Viz-Lasheras0Alberto Gómez-Carballa1Jacobo Pardo-Seco2Xabier Bello3Irene Rivero-Calle4Ana Isabel Dacosta5Myrsini Kaforou6Dominic Habgood-Coote7Aubrey J. Cunnington8Marieke Emonts9Jethro A. Herberg10Victoria J. Wright11Enitan D. Carrol12Stephane C. Paulus13Werner Zenz14Daniela S. Kohlfürst15Michiel Van der Flier16Ronald de Groot17Luregn J. Schlapbach18Philipp Agyeman19Andrew J. Pollard20Colin Fink21Taco T. Kuijpers22Suzanne Anderson23Cristina Calvo24María del Carmen Martínez-Padilla25Ana Pérez-Aragón26Esteban Gómez-Sánchez27Juan Valencia-Ramos28Francisco Giménez-Sánchez29Paula Alonso-Quintela30Laura Moreno-Galarraga31Ulrich von Both32Marko Pokorn33Dace Zavadska34María Tsolia35Clementien L. Vermont36Henriëtte A. Moll37Michael Levin38Federico Martinón-Torres39Antonio Salas40Unidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and Genética de Poblaciones en Biomedicina (GenPoB) Research Group, Instituto de Investigación Sanitaria (IDIS), 15706 Hospital Clínico Universitario de Santiago (SERGAS), Galicia, Spain; Genetics, Vaccines and Infections Research Group (GenViP), Instituto de Investigación Sanitaria de Santiago, 15706 Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), Madrid, SpainUnidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and Genética de Poblaciones en Biomedicina (GenPoB) Research Group, Instituto de Investigación Sanitaria (IDIS), 15706 Hospital Clínico Universitario de Santiago (SERGAS), Galicia, Spain; Genetics, Vaccines and Infections Research Group (GenViP), Instituto de Investigación Sanitaria de Santiago, 15706 Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), Madrid, SpainUnidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and Genética de Poblaciones en Biomedicina (GenPoB) Research Group, Instituto de Investigación Sanitaria (IDIS), 15706 Hospital Clínico Universitario de Santiago (SERGAS), Galicia, Spain; Genetics, Vaccines and Infections Research Group (GenViP), Instituto de Investigación Sanitaria de Santiago, 15706 Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), Madrid, SpainUnidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and Genética de Poblaciones en Biomedicina (GenPoB) Research Group, Instituto de Investigación Sanitaria (IDIS), 15706 Hospital Clínico Universitario de Santiago (SERGAS), Galicia, Spain; Genetics, Vaccines and Infections Research Group (GenViP), Instituto de Investigación Sanitaria de Santiago, 15706 Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), Madrid, SpainGenetics, Vaccines and Infections Research Group (GenViP), Instituto de Investigación Sanitaria de Santiago, 15706 Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), Madrid, Spain; Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 15706 Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Galicia, SpainGenetics, Vaccines and Infections Research Group (GenViP), Instituto de Investigación Sanitaria de Santiago, 15706 Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), Madrid, Spain; Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 15706 Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Galicia, SpainDepartment of Infectious Disease, Imperial College London, London W2 1PG, UKDepartment of Infectious Disease, Imperial College London, London W2 1PG, UKDepartment of Infectious Disease, Imperial College London, London W2 1PG, UKGreat North Children’s Hospital, Paediatric Immunology, Infectious Diseases & Allergy, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; NIHR Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Trust and Newcastle University, Newcastle upon Tyne NE4 5PL, UKDepartment of Infectious Disease, Imperial College London, London W2 1PG, UKDepartment of Infectious Disease, Imperial College London, London W2 1PG, UKDepartment of Infectious Diseases, Alder Hey Children’s NHS Foundation Trust, Liverpool L12 2AP, UK; Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UKDepartment of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UKDepartment of General Paediatrics, Medical University of Graz, Graz, Auenbruggerplatz 34/2 8036, Graz, AustriaDepartment of General Paediatrics, Medical University of Graz, Graz, Auenbruggerplatz 34/2 8036, Graz, AustriaPediatric Infectious Diseases and Immunology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht 3508 AB, the Netherlands; Pediatric Infectious Diseases and Immunology, Amalia Children’s Hospital, and Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen 6500 HB, the NetherlandsPediatric Infectious Diseases and Immunology, Amalia Children’s Hospital, and Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen 6500 HB, the NetherlandsDepartment of Intensive Care and Neonatology, and Children’s Research Center, University Children’s Hospital Zürich, University of Zürich, Zürich, SwitzerlandDepartment of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandDepartment of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UKMicropathology Ltd, University of Warwick, Warwick CV4 7EZ, UKDivision of Pediatric Immunology, Rheumatology and Infectious diseases, Emma Children’s Hospital, Amsterdam Univiersyt Medical Center (Amsterdam UMC), Amsterdam 1105 AZ, the NetherlandsMedical Research Council Unit at the London School of Hygiene & Tropical Medicine, Banjul, The GambiaGeneral Pediatrics, Infectious and Tropical Diseases Department, Hospital La Paz, 28046 Madrid, Spain; La Paz Research Institute (IdiPAZ), 28029 Madrid, Spain; Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain; Red de Investigación Traslacional en Infectología Pediátrica (RITIP), Madrid, SpainUnidad de Cuidados Intensivos Pediátricos, Complejo Hospitalario de Jaen, Jaen, SpainHospital Universitario Virgen de las Nieves, Servicio de Pediatría, Granada, SpainDepartment of Pediatric Intensive Care Unit, Hospital Universitario de Burgos, Burgos, SpainDepartment of Pediatric Intensive Care Unit, Hospital Universitario de Burgos, Burgos, SpainInstituto Hispalense de Pediatría, Instituto Balmis de Vacunas, Almería, SpainNeonatal Intensive Care Unit, Complejo Asistencial Universitario de León, León, SpainDepartment of Pediatrics, Complejo Hospitalario de Navarra, Servicio Navarro de Salud, Pamplona, Spain; IdiSNA (Instituto de Investigación Sanitaria de Navarra), Navarra Institute for Health Research, Pamplona, SpainInfectious Diseases, Department of Pediatrics, Dr von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, GermanyDivision of Paediatrics, University Medical Centre Ljubljana and Medical Faculty, University of Ljubljana, Ljubljana, SloveniaChildren’s Clinical University Hospital, Rīga Stradins University, Rïga, LatviaSecond Department of Paediatrics, National and Kapodistrian University of Athens (NKUA), School of Medicine, Panagiotis & Aglaia, Kyriakou Children’s Hospital, Athens, GreeceDepartment of Pediatrics, Erasmus MC, Rotterdam, the NetherlandsDepartment of Pediatrics, Erasmus MC, Rotterdam, the NetherlandsDepartment of Infectious Disease, Imperial College London, London W2 1PG, UKGenetics, Vaccines and Infections Research Group (GenViP), Instituto de Investigación Sanitaria de Santiago, 15706 Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), Madrid, Spain; Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 15706 Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Galicia, SpainUnidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, and Genética de Poblaciones en Biomedicina (GenPoB) Research Group, Instituto de Investigación Sanitaria (IDIS), 15706 Hospital Clínico Universitario de Santiago (SERGAS), Galicia, Spain; Genetics, Vaccines and Infections Research Group (GenViP), Instituto de Investigación Sanitaria de Santiago, 15706 Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), Madrid, Spain; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004225000069PediatricsDiagnosticsBody substance sampleClinical microbiologyTranscriptomics
spellingShingle Sandra Viz-Lasheras
Alberto Gómez-Carballa
Jacobo Pardo-Seco
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
Michiel Van der Flier
Ronald de Groot
Luregn J. Schlapbach
Philipp Agyeman
Andrew J. Pollard
Colin Fink
Taco T. Kuijpers
Suzanne Anderson
Cristina Calvo
María del Carmen Martínez-Padilla
Ana Pérez-Aragón
Esteban Gómez-Sánchez
Juan Valencia-Ramos
Francisco Giménez-Sánchez
Paula Alonso-Quintela
Laura Moreno-Galarraga
Ulrich von Both
Marko Pokorn
Dace Zavadska
María Tsolia
Clementien L. Vermont
Henriëtte A. Moll
Michael Levin
Federico Martinón-Torres
Antonio Salas
A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia
iScience
Pediatrics
Diagnostics
Body substance sample
Clinical microbiology
Transcriptomics
title A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia
title_full A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia
title_fullStr A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia
title_full_unstemmed A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia
title_short A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia
title_sort 5 transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia
topic Pediatrics
Diagnostics
Body substance sample
Clinical microbiology
Transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004225000069
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