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Published on: February 17, 2023
Evolution of multiple omics approaches to define pathophysiology of pediatric acute respiratory distress syndrome
Jane E Whitney1,2, In-Hee Lee3, Ji-Won Lee4
1Medical Critical Care, Pediatrics, Boston Children's Hospital, Boston, United States.
Insights
Pediatric acute respiratory distress syndrome (PARDS) needs targeted therapies. New single-cell RNA sequencing methods can reveal molecular mechanisms for developing effective treatments for this critical illness in children.
Area of Science:
- Critical care medicine
- Pediatric pulmonology
- Molecular biology
Background:
- Pediatric acute respiratory distress syndrome (PARDS) is a severe, life-threatening condition in critically ill children lacking specific treatments.
- Understanding the complex pathobiology involving lung epithelial injury, vascular endothelial activation, and systemic immune responses is crucial for developing targeted therapies.
- Current research faces limitations due to a scarcity of pediatric-specific omics data and multi-tissue analyses.
Purpose of the Study:
- To synthesize current literature on PARDS molecular mechanisms.
- To analyze publicly available genomic data for candidate gene associations with PARDS phenotypes across various tissues and cell types.
- To integrate findings from recent single-cell RNA sequencing (scRNA-seq) studies.
Main Methods:
- Literature synthesis on PARDS molecular mechanisms.
- Bioinformatic analysis of public genomic databases to identify candidate genes linked to PARDS phenotypes.
- Integration of scRNA-seq data to examine cellular and tissue-level pathobiology.
Main Results:
- Identification of candidate genes associated with PARDS phenotypes across multiple tissues and cell types.
- Integration of multi-omics data, including scRNA-seq, provides a comprehensive view of PARDS pathobiology.
- Highlighting the limitations of current omics studies in pediatric populations.
Conclusions:
- Novel profiling techniques like scRNA-seq are essential for unbiased, comprehensive evaluation of PARDS pathophysiological mechanisms.
- Employing advanced methods like scRNA-seq is critical for uncovering molecular targets for novel pharmacotherapies.
- Further research utilizing scRNA-seq is recommended to advance the development of targeted treatments for PARDS.
Abstract:
Pediatric acute respiratory distress syndrome (PARDS), though both common and deadly in critically ill children, lacks targeted therapies. The development of effective pharmacotherapies has been limited, in part, by lack of clarity about the pathobiology of pediatric ARDS. Epithelial lung injury, vascular endothelial activation, and systemic immune activation are putative drivers of this complex disease process. Prior studies have used either hypothesis-driven (e.g., candidate genes and proteins, in vitro investigations) or unbiased (e.g., genome-wide association, transcriptomic, metabolomic) approaches to predict clinical outcomes and to define subphenotypes. Advances in multiple omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, have permitted more comprehensive investigation of PARDS pathobiology. However, omics studies have been limited in children compared to adults, and analyses across multiple tissue types are lacking. Here, we synthesized existing literature on the molecular mechanism of PARDS, summarized our interrogation of publicly available genomic databases to determine the association of candidate genes with PARDS phenotypes across multiple tissues and cell types, and integrated recent studies that used single-cell RNA sequencing (scRNA-seq). We conclude that novel profiling methods such as scRNA-seq, which permits more comprehensive, unbiased evaluation of pathophysiological mechanisms across tissue and cell types, should be employed to investigate the molecular mechanisms of PRDS toward the goal of identifying targeted therapies.
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