A genomewide association study for bronchopulmonary dysplasia using DNA pooling
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE22284 | GEO | 2011/11/22
SECONDARY ACCESSION(S): PRJNA127429
REPOSITORIES: GEO
Similar Datasets
Project description:Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in premature infants. Recent studies have highlighted the contribution of genetic factors to BPD susceptibility. Our aim was to identify the genetic variants associated to BPD, through a genomewide association study. Two discovery series were performed, using a DNA pooling-based strategy in Caucasian and black African neonates. DNA pooling studies were performed in two discovery series. The first discovery series was made up of 22 Caucasian infants with BPD and 76 Caucasian controls. The second discovery series was composed of 21 black African infants with BPD and 86 black African controls. Equimolar amounts of each DNA sample were then added to either the case or control pool, for each series. To control for experimental errors, several independent sets of pools were constructed. Concerning the Caucasian series, 3 sets of identical pools were constructed with one made in double quantity in order to hybridize it twice, which led to 4 independent replicates. Concerning the black African series, 4 sets of identical pools were constructed and each was hybridized once, leading also to 4 independent replicates. Genotyping was performed using the Infinium II Illumina HumanHap300 Genotyping BeadChip array for the Caucasian population and the Illumina HumanHap650Y array for the black African population. Each replicate was hybridized once which led to 4 arrays for each case and control pools and for each population. A total of 16 arrays were performed. technical replicate: Sample 1, Sample 2, Sample 3, Sample 4 technical replicate: Sample 5, Sample 6, Sample 7, Sample 8 technical replicate: Sample 9, Sample 10, Sample 11, Sample 12 technical replicate: Sample 13, Sample 14, Sample 15, Sample 16
2011-11-22 | E-GEOD-22284 | biostudies-arrayexpress
Project description:Current techniques to diagnose and/or monitor critically ill neonates with bronchopulmonary dysplasia (BPD) require invasive sampling of body fluids, which can affect the health status of these frail neonate. We tested our hypotheses 1) it is feasible to use early urine samples from extremely low gestational age newborns at risk for bronchopulmonary dysplasia for proteomics, and 2) urine proteomics can confirm previously identified proteins and biomarkers associated with BPD without invasive sample collection. We developed a robust high throughput urine proteomics methodology that requires only 50 microliters of urine. We validated the methodology on urine collected within 72 hours of birth. Urine samples were collected from extremely low gestational age newborns (ELGANS) (gestational age (26 + 1.2) weeks) admitted to a single Neonatal Intensive Care Unit(NICU); half of whom eventually developed BPD, while the other half served as controls. Our high throughput urine proteomics approach clearly identified several BPD-associated changes in the urine proteome recapitulating expected blood proteome changes. Interestingly, sixteen identified urinary proteins are known targets of drugs approved by the Food and Drug Administration (FDA). Urine proteomics can be used for prediction of BPD risk. In addition to identifying numerous proteins implicated in BPD pathophysiology, previously found in invasively collected blood, tracheal aspirate, and broncho-alveolar lavage, urine proteomics also suggested novel potential therapeutic targets. Ease of access to urine for sequential proteomic evaluations could also allow for longitudinal monitoring of disease progression and impact of therapeutic intervention.
2022-04-04 | PXD028895 | Pride
Project description:Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD haves been increased. Therapeutic options are limited for prevention and treatment. This study was designed to explore differentially expressed genes associated with BPD. Cord blood mRNA from preterm neonates that went on to develop BPD (n = 6) or not (nonBPD, n = 17) was applied to Illumina HumanHT-12 arrays, we identify differentially expressed genes associated with BPD.
2022-05-05 | GSE188944 | GEO
Project description:Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD haves been increased. Therapeutic options are limited for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight and estímate blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD. Cord blood DNA from preterm neonates that went on to develop BPD (n = 14) or not (nonBPD, n = 93) was applied to Illumina 450K methylation arrays. Using DNA methylation analysis of cord blood DNA, we investigated association of GA and birth weight with the estimated distribution of cord blood cell types, particularly the nucleated red blood cell (NRBC) in a pilot-size cohort of preterm infants with or without BPD. We describe changes in methylation-based estimates of blood cell-type composition in relation to GA and birth weight. After adjusting for covariates (GA, birth weight, cell type proportions, etc.) we identify differentially methylated CpGs and genes associated with BPD.
2022-05-05 | GSE188949 | GEO
Project description:In order to study the gene expression changes in neonatal bronchopulmonary dysplasia (BPD) induced by hyperoxia, we used a rat model to detect the gene expression changes in the control group (A) and hyperoxia group (O) after birth.
2022-08-29 | GSE212098 | GEO
Project description:Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD haves been increased. Therapeutic options are limited for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight and estímate blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD. Peripheral blood DNA (at days 14 and 28) from preterm neonates that went on to develop BPD (n = 14) or not (nonBPD, n = 93) was applied to Illumina EPIC methylation arrays. Using DNA methylation analysis of cord blood DNA, we investigated association of GA and birth weight with the estimated distribution of cord blood cell types, particularly the nucleated red blood cell (NRBC) in a pilot-size cohort of preterm infants with or without BPD. We describe changes in methylation-based estimates of blood cell-type composition in relation to GA and birth weight. After adjusting for covariates (GA, birth weight, cell type proportions, etc.) we identify differentially methylated CpGs and genes associated with BPD at different time points.
2023-07-05 | GSE225313 | GEO
Project description:Bronchopulmonary dysplasia (BPD) remains the most frequent chronic lung disease among infants, which involves multifactorial pathogenesis. Necroptosis represents a caspase-independent mode of programmed cell death, and its deregulation associates with lung diseases, but the mechanisms of necroptosis during BPD are indistinct. This work was conducted for unveiling the post-transcriptional regulatory mechanisms of necroptosis in BPD.
2024-02-21 | GSE219156 | GEO
Project description:Oxidative stress (OS), inflammation, and endoplasmic reticulum (ER) stress sequentially occur in the rat model of hyperoxia (HOX) induced bronchopulmonary dysplasia (BPD), and they all increase DNA damage. Tumor suppressors increase after DNA damage, followed by apoptosis or cellular senescence when the damage becomes irreparable. Although cellular senescence contributes to wound healing, its persistence will inhibit growth potential. Therefore, we hypothesized that the persistence of cellular senescence plays a role in BPD progression. We detected evidence of increased cellular senescence in rat and human BPD lungs. Foxo4-p53 binding was increased in BPD rat lungs, and inhibition of this binding attenuated BPD severity, indicating that such binding contributes to BPD's cellular senescence. Treatment with tauroursodeoxycholic acid (TUDCA) decreases ER stress. N-Acetyl-lysyltyrosylcysteine-amide (KYC) reduced toxic oxidant production by myeloperoxidase (MPO) and subsequent OS and inflammation. Both agents effectively decreased cellular senescence. Concomitantly, alveolar complexity and the number of type 2 alveolar cells increased, indicating that MPO-mediated OS and ER stress preceded cellular senescence in BPD rat pup lungs. These data suggest that cellular senescence plays an essential role in BPD progression. Reducing MPO toxic oxidant production, ER stress, and attenuating cellular senescence are potential therapeutic strategies for halting BPD progression. Using multiomic data to investigate the role of cellular senescence in the development of BPD in rat model.
2024-01-01 | GSE223745 | GEO
Project description:Bronchopulmonary Dysplasia (BPD) is a disease of prematurity related to the arrest of normal lung development. The objective of this study was to perform whole lung proteomics to identify proteins and pathways differentially regulated in BPD in early childhood. The proteomes of biopsies from pediatric human donors aged 1.3 to 3 years were classified based on history of prematurity and histopathologic severity of "Healed" BPD [hBPD] (N=3) and "Established" BPD [eBPD] (N=3) with respective full term age-matched controls (N=6). Samples were analyzed using aTMT16plex labelling strategy. Code employed to perform the statistics is available at https://github.com/GeremyClair/Proteome_analysis_of_a_human_donor_cohort_to_study_bronchiopulmonary_displasia
2023-03-15 | MSV000091493 | MassIVE
Project description:Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (Adm), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which Adm influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice. Bulk RNA sequencing of Adm-sufficient (wild-type or Adm+/+) and Adm-haplodeficient (Adm+/-) mice lungs, integrated with single-cell RNA sequencing data, revealed distinct gene expression patterns and cell type alterations associated with Adm deficiency and LPS exposure. Notably, computational integration with cell atlas data revealed that Adm-haplodeficient mouse lungs exhibited gene expression signatures characteristic of increased inflammation, natural killer (NK) cell frequency and decreased endothelial cell and type II pneumocyte frequency. Furthermore, in silico human BPD patient data analysis supported our cell type frequency finding, highlighting elevated NK cells in BPD infants. These results underscore the protective role of Adm in experimental BPD and emphasize that it is a potential therapeutic target for BPD infants with an inflammatory phenotype.
2024-06-17 | GSE264612 | GEO