iScience (Feb 2025)
A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia
- 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
Affiliations
- Sandra Viz-Lasheras
- Unidade 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
- Alberto Gómez-Carballa
- Unidade 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
- Jacobo Pardo-Seco
- Unidade 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
- Xabier Bello
- Unidade 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
- Irene Rivero-Calle
- 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; Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 15706 Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Galicia, Spain
- Ana Isabel Dacosta
- 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; Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 15706 Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Galicia, Spain
- Myrsini Kaforou
- Department of Infectious Disease, Imperial College London, London W2 1PG, UK
- Dominic Habgood-Coote
- Department of Infectious Disease, Imperial College London, London W2 1PG, UK
- Aubrey J. Cunnington
- Department of Infectious Disease, Imperial College London, London W2 1PG, UK
- Marieke Emonts
- Great 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, UK
- Jethro A. Herberg
- Department of Infectious Disease, Imperial College London, London W2 1PG, UK
- Victoria J. Wright
- Department of Infectious Disease, Imperial College London, London W2 1PG, UK
- Enitan D. Carrol
- Department 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, UK
- Stephane C. Paulus
- Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK
- Werner Zenz
- Department of General Paediatrics, Medical University of Graz, Graz, Auenbruggerplatz 34/2 8036, Graz, Austria
- Daniela S. Kohlfürst
- Department of General Paediatrics, Medical University of Graz, Graz, Auenbruggerplatz 34/2 8036, Graz, Austria
- Michiel Van der Flier
- Pediatric 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 Netherlands
- Ronald de Groot
- 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 Netherlands
- Luregn J. Schlapbach
- Department of Intensive Care and Neonatology, and Children’s Research Center, University Children’s Hospital Zürich, University of Zürich, Zürich, Switzerland
- Philipp Agyeman
- Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Andrew J. Pollard
- Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK
- Colin Fink
- Micropathology Ltd, University of Warwick, Warwick CV4 7EZ, UK
- Taco T. Kuijpers
- Division of Pediatric Immunology, Rheumatology and Infectious diseases, Emma Children’s Hospital, Amsterdam Univiersyt Medical Center (Amsterdam UMC), Amsterdam 1105 AZ, the Netherlands
- Suzanne Anderson
- Medical Research Council Unit at the London School of Hygiene & Tropical Medicine, Banjul, The Gambia
- Cristina Calvo
- General 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, Spain
- María del Carmen Martínez-Padilla
- Unidad de Cuidados Intensivos Pediátricos, Complejo Hospitalario de Jaen, Jaen, Spain
- Ana Pérez-Aragón
- Hospital Universitario Virgen de las Nieves, Servicio de Pediatría, Granada, Spain
- Esteban Gómez-Sánchez
- Department of Pediatric Intensive Care Unit, Hospital Universitario de Burgos, Burgos, Spain
- Juan Valencia-Ramos
- Department of Pediatric Intensive Care Unit, Hospital Universitario de Burgos, Burgos, Spain
- Francisco Giménez-Sánchez
- Instituto Hispalense de Pediatría, Instituto Balmis de Vacunas, Almería, Spain
- Paula Alonso-Quintela
- Neonatal Intensive Care Unit, Complejo Asistencial Universitario de León, León, Spain
- Laura Moreno-Galarraga
- Department 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, Spain
- Ulrich von Both
- Infectious Diseases, Department of Pediatrics, Dr von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany
- Marko Pokorn
- Division of Paediatrics, University Medical Centre Ljubljana and Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
- Dace Zavadska
- Children’s Clinical University Hospital, Rīga Stradins University, Rïga, Latvia
- María Tsolia
- Second Department of Paediatrics, National and Kapodistrian University of Athens (NKUA), School of Medicine, Panagiotis & Aglaia, Kyriakou Children’s Hospital, Athens, Greece
- Clementien L. Vermont
- Department of Pediatrics, Erasmus MC, Rotterdam, the Netherlands
- Henriëtte A. Moll
- Department of Pediatrics, Erasmus MC, Rotterdam, the Netherlands
- Michael Levin
- Department of Infectious Disease, Imperial College London, London W2 1PG, UK
- Federico Martinón-Torres
- 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; Translational Pediatrics and Infectious Diseases, Department of Pediatrics, 15706 Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Galicia, Spain
- Antonio Salas
- Unidade 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 author
- Journal volume & issue
-
Vol. 28,
no. 2
p. 111747
Abstract
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.
