Organismal metagenomes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA766788 | ENA |
REPOSITORIES: ENA
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2009-07-31 | E-MTAB-12 | biostudies-arrayexpress
Project description:BACKGROUND. Lower respiratory tract infection (LRTI) is a leading cause of death in children worldwide. LRTI diagnosis is challenging since non-infectious respiratory illnesses appear clinically similar and existing microbiologic tests are often falsely negative or detect incidentally-carried microbes common in children. These challenges result in antimicrobial overuse and adverse patient outcomes. Lower airway metagenomics has the potential to detect host and microbial signatures of LRTI. Whether it can be applied at scale and in a pediatric population to enable improved diagnosis and precision treatment remains unclear. METHODS. We used tracheal aspirate RNA-sequencing to profile host gene expression and respiratory microbiota in 261 children with acute respiratory failure. We developed a random forest gene expression classifier for LRTI by training on patients with an established diagnosis of LRTI (n=117) or of non-infectious respiratory failure (n=50). We then developed a classifier that integrates the: i) host LRTI probability, ii) abundance of respiratory viruses, and iii) dominance in the lung microbiome of bacteria/fungi considered pathogenic by a rules-based algorithm. RESULTS. The host classifier achieved a median AUC of 0.967 by 5-fold cross-validation, driven by activation markers of T cells, alveolar macrophages and the interferon response. The integrated classifier achieved a median AUC of 0.986 and significantly increased the confidence of patient classifications. When applied to patients with an uncertain diagnosis (n=94), the integrated classifier indicated LRTI in 52% of cases and nominated likely causal pathogens in 98% of those. CONCLUSIONS. Lower airway metagenomics enables accurate LRTI diagnosis and pathogen identification in a heterogeneous cohort of critically ill children through integration of host, pathogen, and microbiome features.
2022-12-06 | GSE212532 | GEO
Project description:We preformed a systems biological assessment of lower respiratory tract host immune responses and microbiome dynamics in COVD-19 patients, using bulk RNA-sequencing, single-cell RNA sequencing, and techniques, and microbiome analysis. Are focus was on differential gene expression in severe COVID-19 patients who developed ventilator associated pneumonia (VAP) during their course versus severe COVID-19 patients who did not develop VAP. We found early impairment in antibacterial immune signaling in patients two or more weeks prior to the development of VAP, compared to COVID-19 patients who did not develop VAP. There was no signficant difference in viral load, but an association of disruption in lung microbiome by alpha and beta diversity metrics was also found.
2021-03-03 | GSE168018 | GEO
Project description:We preformed a systems biological assessment of lower respiratory tract host immune responses and microbiome dynamics in COVD-19 patients, using bulk RNA-sequencing, single-cell RNA sequencing, and techniques, and microbiome analysis. Are focus was on differential gene expression in severe COVID-19 patients who developed ventilator associated pneumonia (VAP) during their course versus severe COVID-19 patients who did not develop VAP. We found early impairment in antibacterial immune signaling in patients two or more weeks prior to the development of VAP, compared to COVID-19 patients who did not develop VAP. There was no signficant difference in viral load, but an association of disruption in lung microbiome by alpha and beta diversity metrics was also found.
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Project description:The respiratory epithelium is the body’s first line of defense to pathogens, pollutants, and other potentially injurious agents that can be inhaled. Sampling the upper respiratory tract is becoming a widely used technique in the clinic to examine the molecular changes in the diseased airway; however, it is unclear as to whether the responses in the upper respiratory tract (i.e. the nasal turbinates) reflect the changes that occur in the lower respiratory tract (i.e. trachea and lungs). Here, we assessed the responses to poly I:C, a synthetic double-stranded RNA molecule that is meant to mimic the acute effects of a viral infection, in both the upper and lower respiratory tracts of cynomolgus macaques. To do this, we compared the in vivo response after a nasal poly I:C challenge in a nasal scrape samples (performed using a nasal curette) to responses that occurred after ex vivo poly I:C stimulation in nasal scrapes, tracheal epithelial brushings, and lung tissue explants in non-human primates.
2015-10-11 | GSE41672 | GEO
Project description:The respiratory epithelium is the body’s first line of defense to pathogens, pollutants, and other potentially injurious agents that can be inhaled. Sampling the upper respiratory tract is becoming a widely used technique in the clinic to examine the molecular changes in the diseased airway; however, it is unclear as to whether the responses in the upper respiratory tract (i.e. the nasal turbinates) reflect the changes that occur in the lower respiratory tract (i.e. trachea and lungs). Here, we assessed the responses to poly I:C, a synthetic double-stranded RNA molecule that is meant to mimic the acute effects of a viral infection, in both the upper and lower respiratory tracts of cynomolgus macaques. To do this, we compared the in vivo response after a nasal poly I:C challenge in a nasal scrape samples (performed using a nasal curette) to responses that occurred after ex vivo poly I:C stimulation in nasal scrapes, tracheal epithelial brushings, and lung tissue explants in non-human primates.
2015-10-11 | GSE41671 | GEO