Detection Of Excess Rare Damaging Variants In Surfactant Associated Genes Among Infants With Respiratory Distress Syndrome Using Pooled Next Generation Sequencing

Author(s):  
Jennifer A. Wambach ◽  
Daniel J. Wegner ◽  
Sarah Robison ◽  
Kelsey DePass ◽  
Todd Druley ◽  
...  
PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9623
Author(s):  
Peng Zhang ◽  
Yan Chen ◽  
Shuyun Li ◽  
Chaoliang Li ◽  
Shuang Zhang ◽  
...  

Background Metagenome next-generation sequencing (mNGS) is a valuable diagnostic tool that can be used for the identification of early pathogens of acute respiratory distress syndrome (ARDS) in severe pneumonia. Little is known about the use of this technology in clinical application and the evaluation of the prognostic value of ARDS. Methods We performed a retrospective cohort study of patients with ARDS caused by severe pneumonia. Samples were collected from patients in the intensive care unit (ICU) of Jiangmen Central Hospital from January 2018 to August 2019. The no-next generation sequencing (NGS) group was composed of patients given conventional microbiological tests to examine sputum, blood, or bronchoalveolar lavage fluid. The NGS group was composed of patients tested using mNGS and conventional microbiological tests. We evaluated the etiological diagnostic effect and clinical prognostic value of mNGS in patients with ARDS caused by severe pneumonia. Results The overall positive rate (91.1%) detected by the mNGS method was significantly higher than that of the culture method (62.2%, P = 0.001), and antibody plus polymerase chain reaction (28.9%, P < 0.001). Following adjustment of the treatment plan based on microbial testing results, the Acute Physiology and Chronic Health Evaluation-II (APACHE II) score of the NGS group was lower than that of the no-NGS group 7 days after treatment (P < 0.05). The 28-day mortality rate of the NGS group was significantly lower than that of the no-NGS group (P < 0.05). Longer ICU stay, higher APACHE II score and sequential organ failure assessment score were risk factors for the death of ARDS, and adjusting the medication regimen based on mNGS results was a protective factor. The detection of mNGS can significantly shorten the ICU stay of immunosuppressed patients (P < 0.01), shorten the ventilation time (P < 0.01), and reduce the ICU hospitalization cost (P < 0.05). Conclusions Metagenome next-generation sequencing is a valuable tool to determine the etiological value of ARDS caused by severe pneumonia to improve diagnostic accuracy and prognosis for this disease. For immunosuppressed patients, mNGS technology can be used in the early stage to provide more diagnostic evidence and guide medications.


2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Qi-Quan Wan ◽  
Di Wu ◽  
Qi-Fa Ye

Up until now, the regulation mechanism at the level of gene during lipopolysaccharide- (LPS-) induced acute respiratory distress syndrome (ARDS) remains unclear. The discovery of differentially expressed genes (DEGs) between LPS-induced ARDS rats and normal rats by next-generation RNA sequencing analysis is of particular interest for the current study. These DEGs may help clinical diagnosis of ARDS and facilitate the selection of the optimal treatment strategy. Randomly, 20 rats were equally divided into 2 groups, the control group and the LPS group. Three rats from each group were selected at random for RNA sequencing analysis. Sequence reads were obtained from Illumina HiSeq4000 and mapped onto the rat reference genome RN6 using Hisat2. We identified 5244 DEGs (Fold_Change > 1.5, and P<0.05) in the lung tissues from LPS-treated rats compared with normal rats, including 1413 upregulated and 3831 downregulated expressed genes. Lots of chemokine family members were among the most upregulated genes in LPS group. Gene ontology (GO) analysis revealed that almost all of the most enriched and meaningful biological process terms were mainly involved in the functions like immune-inflammation response and the pathways like cytokine-cytokine receptor interaction. We also found that, as for GO molecular function terms, the enriched terms were mainly related to chemokines and cytokines. DEGs with fold change over 100 were verified by quantitative real-time polymerase chain reaction and reanalyzed by gene-gene coexpression network, and the results elucidated central roles of chemokines in LPS-induced ARDS. Our results revealed some new biomarkers for uncovering mechanisms and processes of ARDS.


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