A Data Report on the Curation and Development of a Database of Genes for Acute Respiratory Distress Syndrome

Quintanilla, Erick; Diwa, Kimberly; Nguyen, Ashley; Vu, Lavang; Toby, Inimary T.

doi:10.3389/fgene.2021.750568

Cited by 4 publications

(6 citation statements)

References 16 publications

(25 reference statements)

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“…We descriptively compared the overlap between this list and the MAIC-ranked gene list. Similar comparisons were made between the ARDS MAIC results and the gene set in the ARDS Database of Genes 55 and a prior MAIC of SARS-CoV-2 host genomics 11 .…”

Section: Methodsmentioning

confidence: 96%

“…A detailed description of our search strategy and eligibility criteria is provided in the Supplementary Methods. Briefly, we searched MEDLINE, Embase, bioRxiv, medRxiv, the ARDS Database of Genes 55 , and the NCBI Gene Expression Omnibus from inception to April 1 st , 2023 without language restrictions. We also performed single-level backwards and forwards citation searches using SpiderCite 79 and hand-searched recent review articles 80–83 .…”

Section: Methodsmentioning

confidence: 99%

“…To place our meta-analysis results in context, we evaluated the overlap between the genes prioritised by MAIC and those from two established resources: BioLitMine 54 , using an ARDS MeSH search, and the ARDS Database of Genes 55 (Fig. S3a and Fig.…”

Section: Comparison With Existing Ards Sources and Covid-19mentioning

confidence: 99%

Section: Search Strategy and Selection Criteriamentioning

confidence: 99%

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The genomic landscape of Acute Respiratory Distress Syndrome: a meta-analysis by information content of genome-wide studies of the host response

Millar,

Clohisey-Hendry,

McMannus

et al. 2024

Preprint

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Acute respiratory distress syndrome (ARDS) is a clinically defined syndrome of acute hypoxaemic respiratory failure secondary to non-cardiogenic pulmonary oedema. It arises from a diverse set of triggers and encompasses marked biological heterogeneity, complicating efforts to develop effective therapies. An extensive body of recent work (including transcriptomics, proteomics, and genome-wide association studies) has sought to identify proteins/genes implicated in ARDS pathogenesis. These diverse studies have not been systematically collated and interpreted. To solve this, we performed a systematic review and computational integration of existing omics data implicating host response pathways in ARDS pathogenesis. We identified 40 unbiased studies reporting associations, correlations, and other links with genes and single nucleotide polymorphisms (SNPs), from 6,856 ARDS patients. We used meta-analysis by information content (MAIC) to integrate and evaluate these data, ranking over 7,000 genes and SNPs and weighting cumulative evidence for association. Functional enrichment of strongly-supported genes revealed cholesterol metabolism, endothelial dysfunction, innate immune activation and neutrophil degranulation as key processes. We identify 51 hub genes, most of which are potential therapeutic targets. To explore biological heterogeneity, we conducted a separate analysis of ARDS severity/outcomes, revealing distinct gene associations and tissue specificity. Our large-scale integration of existing omics data in ARDS enhances understanding of the genomic landscape by synthesising decades of data from diverse sources. The findings will help researchers refine hypotheses, select candidate genes for functional validation, and identify potential therapeutic targets and repurposing opportunities. Our study and the publicly available computational framework represent an open, evolving platform for interpretation of ARDS genomic data.

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Section: Methodsmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Comparison With Existing Ards Sources and Covid-19mentioning

confidence: 99%

Section: Search Strategy and Selection Criteriamentioning

confidence: 99%

See 2 more Smart Citations

The genomic landscape of Acute Respiratory Distress Syndrome: a meta-analysis by information content of genome-wide studies of the host response

Millar,

Clohisey-Hendry,

McMannus

et al. 2024

Preprint

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“…These studies based on IEI show how one or a few variants in immune responserelated genes can have a major impact on host defense, and also show evidence of the importance that IEIs can have in the development of ARDS due to a dysregulated immune response. Surprisingly, there is an overlap of a total of 22 genes (Table 2) between those listed as an IEI in the last update of the International Union of Immunological Societies Expert Committee [112] and the 238 genes of the ARDS-DB prioritized by intensive manual curation efforts combined with machine learning algorithms [113]. In support of the idea that pathogenic mechanisms of IEIs can help to improve our understanding of ARDS pathogenesis, there has been an exponential increase in studies and a constant reinforcement in the common and different clinical characteristics between COVID-19 ARDS and non-COVID-19 ARDS [119,120].…”

Section: Lessons From the Inborn Errors Of Immunity And Covid-19mentioning

confidence: 99%

Genetic Determinants of the Acute Respiratory Distress Syndrome

Suarez-Pajes,

Tosco-Herrera,

Ramirez-Falcon

et al. 2023

JCM

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Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition that arises from multiple causes, including sepsis, pneumonia, trauma, and severe coronavirus disease 2019 (COVID-19). Given the heterogeneity of causes and the lack of specific therapeutic options, it is crucial to understand the genetic and molecular mechanisms that underlie this condition. The identification of genetic risks and pharmacogenetic loci, which are involved in determining drug responses, could help enhance early patient diagnosis, assist in risk stratification of patients, and reveal novel targets for pharmacological interventions, including possibilities for drug repositioning. Here, we highlight the basis and importance of the most common genetic approaches to understanding the pathogenesis of ARDS and its critical triggers. We summarize the findings of screening common genetic variation via genome-wide association studies and analyses based on other approaches, such as polygenic risk scores, multi-trait analyses, or Mendelian randomization studies. We also provide an overview of results from rare genetic variation studies using Next-Generation Sequencing techniques and their links with inborn errors of immunity. Lastly, we discuss the genetic overlap between severe COVID-19 and ARDS by other causes.

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Therapeutic characteristics of alveolar-like macrophages in mouse models of hyperoxia and LPS-induced lung inflammation

Litman,

Bouch,

Litvack

et al. 2024

American Journal of Physiology-Lung Cellular and Molecular Phys

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Acute respiratory distress syndrome (ARDS) is a severe lung disease of high mortality (30-50%). Patients require lifesaving supplemental oxygen therapy; however, hyperoxia can induce pulmonary inflammation and cellular damage. Although alveolar macrophages (AMs) are essential for lung immune homeostasis, they become compromised during inflammatory lung injury. To combat this, stem cell-derived alveolar-like macrophages (ALMs) are a prospective therapeutic for lung diseases like ARDS. Using in vitro and in vivo approaches, we investigated the impact of hyperoxia on murine ALMs during acute inflammation. In vitro, ALMs retained their viability, growth and antimicrobial abilities when cultured at 60% O2, while they die at 90% O2. In contrast, ALMs instilled in mouse lungs remained viable during exposure of mice to 90% O2. The ability of the delivered ALMs to phagocytose Pseudomonas aeruginosa was not impaired by exposure to 60 or 90% O2. Furthermore, ALMs remained immunologically stable in a murine model of LPS-induced lung inflammation when exposed to 60 and 90% O2 and effectively attenuated the accumulation of CD11b+ inflammatory cells in the airways. These results support the potential use of ALMs in ARDS patients receiving supplemental oxygen therapy.

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A Data Report on the Curation and Development of a Database of Genes for Acute Respiratory Distress Syndrome

Cited by 4 publications

References 16 publications

The genomic landscape of Acute Respiratory Distress Syndrome: a meta-analysis by information content of genome-wide studies of the host response

The genomic landscape of Acute Respiratory Distress Syndrome: a meta-analysis by information content of genome-wide studies of the host response

Genetic Determinants of the Acute Respiratory Distress Syndrome

Therapeutic characteristics of alveolar-like macrophages in mouse models of hyperoxia and LPS-induced lung inflammation

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