Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
10
03
2022
accepted:
23
08
2022
pubmed:
21
10
2022
medline:
1
11
2022
entrez:
20
10
2022
Statut:
ppublish
Résumé
We carried out integrated host and pathogen metagenomic RNA and DNA next generation sequencing (mNGS) of whole blood (n = 221) and plasma (n = 138) from critically ill patients following hospital admission. We assigned patients into sepsis groups on the basis of clinical and microbiological criteria. From whole-blood gene expression data, we distinguished patients with sepsis from patients with non-infectious systemic inflammatory conditions using a trained bagged support vector machine (bSVM) classifier (area under the receiver operating characteristic curve (AUC) = 0.81 in the training set; AUC = 0.82 in a held-out validation set). Plasma RNA also yielded a transcriptional signature of sepsis with several genes previously reported as sepsis biomarkers, and a bSVM sepsis diagnostic classifier (AUC = 0.97 training set; AUC = 0.77 validation set). Pathogen detection performance of plasma mNGS varied on the basis of pathogen and site of infection. To improve detection of virus, we developed a secondary transcriptomic classifier (AUC = 0.94 training set; AUC = 0.96 validation set). We combined host and microbial features to develop an integrated sepsis diagnostic model that identified 99% of microbiologically confirmed sepsis cases, and predicted sepsis in 74% of suspected and 89% of indeterminate sepsis cases. In summary, we suggest that integrating host transcriptional profiling and broad-range metagenomic pathogen detection from nucleic acid is a promising tool for sepsis diagnosis.
Identifiants
pubmed: 36266337
doi: 10.1038/s41564-022-01237-2
pii: 10.1038/s41564-022-01237-2
pmc: PMC9613463
doi:
Substances chimiques
RNA
63231-63-0
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1805-1816Subventions
Organisme : NHLBI NIH HHS
ID : K23 HL138461
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL155418
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL140026
Pays : United States
Organisme : NHLBI NIH HHS
ID : F32 HL151117
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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