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A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia
Sandra Viz-Lasheras1,2,3, Alberto Gómez-Carballa1,2,3, Jacobo Pardo-Seco1,2,3
1Unidade 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.
Insights
A new 5-gene blood biomarker signature accurately distinguishes bacterial from viral pneumonia in children. This discovery can improve pediatric pneumonia diagnosis, reducing delays and unnecessary treatments.
Area of Science:
- Pediatric infectious diseases
- Molecular diagnostics
- Transcriptomics
Background:
- Pneumonia is a leading cause of mortality in children under five.
- Current diagnostic methods for pediatric pneumonia can lead to misdiagnosis, resulting in inadequate or unnecessary treatments.
Purpose of the Study:
- To identify host transcriptomic biomarkers in blood to differentiate between viral and bacterial pneumonia in children.
- To develop a diagnostic tool for more accurate pediatric pneumonia classification.
Main Methods:
- RNA sequencing was performed on 192 whole blood samples (38 controls, 154 pneumonia cases).
- A 5-transcript signature (FAM20A, BAG3, TDRD9, MXRA7, KLF14) was identified using logistic regression and random forest models.
- The signature's diagnostic performance was evaluated using area under the curve (AUC) in initial and full validation cohorts.
Main Results:
- A 5-transcript signature demonstrated high accuracy in distinguishing bacterial from viral pneumonia (AUC: 0.95).
- Initial validation in a combined cohort showed an AUC of 0.87.
- Full validation in a separate prospective cohort confirmed the signature's robustness (AUC: 0.92).
Conclusions:
- The identified 5-transcript signature serves as a promising biomarker for differentiating pediatric bacterial and viral pneumonia.
- This transcriptomic signature has the potential to significantly improve diagnostic accuracy, reduce treatment delays, and optimize clinical management of childhood pneumonia.
Abstract:
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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Various factors influence the likelihood of developing pneumonia. Age plays a crucial role, with infants, children under two, and individuals over 65 at increased risk due to their...