Plasma cell-free RNA signatures of inflammatory syndromes in children

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyt...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 121; no. 37; p. e2403897121
Main Authors Loy, Conor J, Servellita, Venice, Sotomayor-Gonzalez, Alicia, Bliss, Andrew, Lenz, Joan S, Belcher, Emma, Suslovic, Will, Nguyen, Jenny, Williams, Meagan E, Oseguera, Miriam, Gardiner, Michael A, Choi, Jong-Ha, Hsiao, Hui-Mien, Wang, Hao, Kim, Jihoon, Shimizu, Chisato, Tremoulet, Adriana H, Delaney, Meghan, DeBiasi, Roberta L, Rostad, Christina A, Burns, Jane C, Chiu, Charles Y, De Vlaminck, Iwijn
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 10.09.2024
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Abstract Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C-two conditions presenting with overlapping symptoms-with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.
AbstractList Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C—two conditions presenting with overlapping symptoms—with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.
Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C-two conditions presenting with overlapping symptoms-with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C-two conditions presenting with overlapping symptoms-with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.
This study provides a proof of concept that circulating RNA in blood plasma can be used to differentiate multiple inflammatory syndromes in children that are difficult to diagnose clinically, as well as provide evidence that circulating RNA in blood plasma can also be used to characterize organ damage using the same assay. Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C—two conditions presenting with overlapping symptoms—with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.
Author Burns, Jane C
Gardiner, Michael A
Hsiao, Hui-Mien
Chiu, Charles Y
Servellita, Venice
Bliss, Andrew
Williams, Meagan E
Belcher, Emma
Choi, Jong-Ha
Tremoulet, Adriana H
DeBiasi, Roberta L
Oseguera, Miriam
Lenz, Joan S
Delaney, Meghan
Rostad, Christina A
Sotomayor-Gonzalez, Alicia
Kim, Jihoon
Loy, Conor J
Nguyen, Jenny
Shimizu, Chisato
De Vlaminck, Iwijn
Suslovic, Will
Wang, Hao
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1A complete list of the members of the Pediatric Emergency Medicine Kawasaki Disease Research Group (PEMKDRG) and the Characterization of Multisystem Inflammatory Syndrome in Children (CHARMS) Study Group is available in the supporting information.
Edited by Y. M. Lo, The Chinese University of Hong Kong, Shatin New Territories, Hong Kong; received February 23, 2024; accepted July 25, 2024
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Snippet Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a...
This study provides a proof of concept that circulating RNA in blood plasma can be used to differentiate multiple inflammatory syndromes in children that are...
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StartPage e2403897121
SubjectTerms Adolescent
Bacterial diseases
Bacterial infections
Bacterial Infections - blood
Bacterial Infections - diagnosis
Biological Sciences
Biomarkers - blood
Cell-Free Nucleic Acids - blood
Cell-Free Nucleic Acids - genetics
Child
Child, Preschool
Children
COVID-19 - complications
Diagnosis
Diagnosis, Differential
Differential diagnosis
Disorders
Endothelium
Female
Humans
Infant
Infections
Inflammation - blood
Injury analysis
Learning algorithms
Machine Learning
Male
Mucocutaneous lymph node syndrome
Mucocutaneous Lymph Node Syndrome - blood
Mucocutaneous Lymph Node Syndrome - diagnosis
Mucocutaneous Lymph Node Syndrome - genetics
Multisystem inflammatory syndrome in children
Nervous system
Pediatrics
Respiratory tract
Systemic Inflammatory Response Syndrome - blood
Systemic Inflammatory Response Syndrome - diagnosis
Viral infections
Virus Diseases - blood
Virus Diseases - diagnosis
Virus Diseases - genetics
Title Plasma cell-free RNA signatures of inflammatory syndromes in children
URI https://www.ncbi.nlm.nih.gov/pubmed/39240972
https://www.proquest.com/docview/3106760558
https://www.proquest.com/docview/3101553499
https://pubmed.ncbi.nlm.nih.gov/PMC11406294
Volume 121
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