Transcriptomic signatures of neonatal acute respiratory distress syndrome in a prospective cohort of respiratory distress

Summary: Neonatal acute respiratory distress syndrome (NARDS) is challenging to differentiate from other respiratory conditions, and gestational age (GA) may influence gene expression. This study characterized whole blood transcriptomic profiles of NARDS in a pilot cohort of 48 neonates with respira...

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Main Authors: Chan Liu, Qing Ai, Jingli Yang, Ying Fan, Wen Jia, Leyu Si, Yuting Yao, Feifan Chen, Shiyue Liu, Yu He, Yuan Shi
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225012684
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author Chan Liu
Qing Ai
Jingli Yang
Ying Fan
Wen Jia
Leyu Si
Yuting Yao
Feifan Chen
Shiyue Liu
Yu He
Yuan Shi
author_facet Chan Liu
Qing Ai
Jingli Yang
Ying Fan
Wen Jia
Leyu Si
Yuting Yao
Feifan Chen
Shiyue Liu
Yu He
Yuan Shi
author_sort Chan Liu
collection DOAJ
description Summary: Neonatal acute respiratory distress syndrome (NARDS) is challenging to differentiate from other respiratory conditions, and gestational age (GA) may influence gene expression. This study characterized whole blood transcriptomic profiles of NARDS in a pilot cohort of 48 neonates with respiratory distress, demonstrating a significant GA-dependent modulation of gene expression. Functional analyses revealed prominent involvement of interferon-related pathways in NARDS, with greater suppression in neonates born before 34 weeks. Immune cell infiltration was observed in term or late preterm neonates but was absent in more preterm cases. Machine learning identified three key predictive genes, among which ALOX15 and PTGDR2 were validated in an independent cohort, with area under the curve ranging from 0.68 to 0.83 across different GAs. The gene changes were also confirmed in a neonatal lipopolysaccharide-induced lung injury mouse model. These findings highlight the potential predictive and therapeutic value of ALOX15 and PTGDR2 for NARDS.
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spelling doaj-art-9b125da12fb04f74b46d6d429e3ab1332025-08-20T03:13:32ZengElsevieriScience2589-00422025-08-0128811300710.1016/j.isci.2025.113007Transcriptomic signatures of neonatal acute respiratory distress syndrome in a prospective cohort of respiratory distressChan Liu0Qing Ai1Jingli Yang2Ying Fan3Wen Jia4Leyu Si5Yuting Yao6Feifan Chen7Shiyue Liu8Yu He9Yuan Shi10Department of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, China; Corresponding authorDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, China; Corresponding authorSummary: Neonatal acute respiratory distress syndrome (NARDS) is challenging to differentiate from other respiratory conditions, and gestational age (GA) may influence gene expression. This study characterized whole blood transcriptomic profiles of NARDS in a pilot cohort of 48 neonates with respiratory distress, demonstrating a significant GA-dependent modulation of gene expression. Functional analyses revealed prominent involvement of interferon-related pathways in NARDS, with greater suppression in neonates born before 34 weeks. Immune cell infiltration was observed in term or late preterm neonates but was absent in more preterm cases. Machine learning identified three key predictive genes, among which ALOX15 and PTGDR2 were validated in an independent cohort, with area under the curve ranging from 0.68 to 0.83 across different GAs. The gene changes were also confirmed in a neonatal lipopolysaccharide-induced lung injury mouse model. These findings highlight the potential predictive and therapeutic value of ALOX15 and PTGDR2 for NARDS.http://www.sciencedirect.com/science/article/pii/S2589004225012684TranscriptomicsMachine learning
spellingShingle Chan Liu
Qing Ai
Jingli Yang
Ying Fan
Wen Jia
Leyu Si
Yuting Yao
Feifan Chen
Shiyue Liu
Yu He
Yuan Shi
Transcriptomic signatures of neonatal acute respiratory distress syndrome in a prospective cohort of respiratory distress
iScience
Transcriptomics
Machine learning
title Transcriptomic signatures of neonatal acute respiratory distress syndrome in a prospective cohort of respiratory distress
title_full Transcriptomic signatures of neonatal acute respiratory distress syndrome in a prospective cohort of respiratory distress
title_fullStr Transcriptomic signatures of neonatal acute respiratory distress syndrome in a prospective cohort of respiratory distress
title_full_unstemmed Transcriptomic signatures of neonatal acute respiratory distress syndrome in a prospective cohort of respiratory distress
title_short Transcriptomic signatures of neonatal acute respiratory distress syndrome in a prospective cohort of respiratory distress
title_sort transcriptomic signatures of neonatal acute respiratory distress syndrome in a prospective cohort of respiratory distress
topic Transcriptomics
Machine learning
url http://www.sciencedirect.com/science/article/pii/S2589004225012684
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