ArticleBMC pulmonary medicine2015
Identification of new biomarkers for Acute Respiratory Distress Syndrome by expression-based genome-wide association study.
Article in BMC pulmonary medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 22 citations in OpenAlex.
- The dual role of thrombospondin-1 in inflammatory regulation during acute respiratory distress syndrome: a mini-review.Frontiers in immunology · 2025Review
- Trimethoprim-sulfamethoxazole acute respiratory distress syndrome requiring lung transplantation.Respirology case reports · 2024Article
- Translational medicine for acute lung injury.Journal of translational medicine · 2024Review
- Multi-omics analysis dissects the genetic architecture of seed coat content in Brassica napus.Genome biology · 2022Article
- Mechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques.Journal of inflammation research · 2022Review
- Nucleotide polymorphism in ARDS outcome: a whole exome sequencing association study.Annals of translational medicine · 2021Article
- Article
- Translational Genomics in Neurocritical Care: a Review.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- Genomics and the Acute Respiratory Distress Syndrome: Current and Future Directions.International journal of molecular sciences · 2019Review
- Negative Regulation of Cytokine Signaling in Immunity.Cold Spring Harbor perspectives in biology · 2018Review
- Host responses to concurrent combined injuries in non-human primates.Journal of inflammation (London, England) · 2017Article
- Identification of lung-specific genes by meta-analysis of multiple tissue RNA-seq data.FEBS open bio · 2016Article
- Using Multi-objective Optimization to Identify Dynamical Network Biomarkers as Early-warning Signals of Complex Diseases.Scientific reports · 2016Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAccumulated to-date gene microarray data on Acute Respiratory Distress Syndrome (ARDS) in the Gene Expression Omnibus (GEO) represent a rich source for identifying new unsuspected targets and mechanisms of ARDS. The recently developed expression-based genome-wide association study (eGWAS) for analysis of GEO data was successfully used for analysis of gene expression of comparatively noncomplex adipose tissue, 75 % of which is represented by adipocytes. Although lung tissue is more heterogenic and does not possess a prevalent cell type for driving gene expression patterns, we hypothesized that eGWAS of ARDS samples will generate biologically meaningful results.
methodsThe eGWAS was conducted according to (Proc Natl Acad Sci U S A 109:7049-7054, 2012) and genes were ranked according to p values of chi-square test.
resultsThe search of GEO retrieved 487 ARDS related entries. These entries were filtered for multiple qualitative and quantitative conditions and 219 samples were selected: mouse n sham/ARDS = 67/92, rat n = 13/13, human cells n = 11/11, canine n = 6/6 with the following ARDS model distributions: mechanical ventilation (MV)/cyclic stretch n = 11; endotoxin (LPS) treatment n = 8; MV + LPS n = 3; distant organ injury induced ARDS n = 3; chemically induced ARDS n = 2; Staphylococcus aureus induced ARDS n = 2; and one experiment each for radiation and shock induced ARDS. The eGWAS of this dataset identified 42 significant (Bonferroni threshold P < 1.55 × 10(-6)) genes. 66.6 % of these genes, were associated previously with lung injury and include the well known ARDS genes such as IL1R2 (P = 4.42 × 10(-19)), IL1β (P = 3.38 × 10(-17)), PAI1 (P = 9.59 × 10(-14)), IL6 (P = 3.57 × 10(-12)), SOCS3 (P = 1.05 × 10(-10)), and THBS1 (P = 2.01 × 10(-9)). The remaining genes were new ARDS candidates. Expression of the most prominently upregulated genes, CLEC4E (P = 4.46 × 10(-14)) and CD300LF (P = 2.31 × 10(-16)), was confirmed by real time PCR. The former was also validated by in silico pathway analysis and the latter by Western blot analysis.
conclusionsOur first in the field application of eGWAS in ARDS and utilization of more than 120 publicly available microarray samples of ARDS not only justified applicability of eGWAS to complex lung tissue, but also discovered 14 new candidate genes which associated with ARDS. Detailed studies of these new candidates might lead to identification of unsuspected evolutionarily conserved mechanisms triggered by ARDS.
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