Evaluating methods for identifying and quantifying <i>Streptococcus pneumoniae</i> co-colonization using next-generation sequencing data
Notice bibliographique
Résumé
Detection of multiple pneumococcal serotype carriage can enhance monitoring of pneumococcal vaccine impact, particularly among high-burden childhood populations. We assessed methods for identifying co-carriage of pneumococcal serotypes from whole-genome sequences. Twenty-four nasopharyngeal samples were collected during community carriage surveillance from healthy children in Blantyre, Malawi, which were then serotyped by microarray. Pneumococcal DNA from culture plate sweeps were sequenced using Illumina MiSeq, and genomic serotyping was carried out using SeroCall and PneumoKITy. Their sensitivity was calculated in reference to the microarray data. Local maxima in the single-nucleotide polymorphism (SNP) density distributions were assessed for their correspondence to the relative abundance of serotypes. Across the 24 individuals, the microarray detected 77 non-unique serotypes, of which 42 occurred at high relative abundance (>10%) (per individual, median, 3; range, 1-6 serotypes). The average sequencing depth was 57X (range: 21X-88X). The sensitivity of SeroCall for identifying high-abundance serotypes was 98% (95% CI, 0.87-1.00), 20% (0.08-0.36) for low abundance (<10%), and 62% (0.50-0.72) overall. PneumoKITy's sensitivity was 86% (0.72-0.95), 20% (0.06-0.32), and 56% (0.42-0.65), respectively. Local maxima in the SNP frequency distribution were highly correlated with the relative abundance of high-abundance serotypes. Six samples were resequenced, and the pooled runs had an average fourfold increase in sequencing depth. This allowed genomic serotyping of two of the previously undetectable seven low-abundance serotypes. Genomic serotyping is highly sensitive for the detection of high-abundance serotypes in samples with co-carriage. Serotype-associated reads may be identified through SNP frequency, and increased read depth can increase sensitivity for low-abundance serotype detection.IMPORTANCEPneumococcal carriage is a prerequisite for invasive pneumococcal disease, which is a leading cause of childhood pneumonia. Multiple carriage of unique pneumococcal serotypes at a single time point is prevalent among high-burden childhood populations. This study assessed the sensitivity of different genomic serotyping methods for identifying pneumococcal serotypes during co-carriage. These methods were evaluated against the current gold standard for co-carriage detection. The results showed that genomic serotyping methods have high sensitivity for detecting high-abundance serotypes in samples with co-carriage, and increasing sequencing depth can increase sensitivity for low-abundance serotypes. These results are important for monitoring vaccine impact, which aims to reduce the prevalence of specific pneumococcal serotypes. By accurately detecting and identifying multiple pneumococcal serotypes in carrier populations, we can better evaluate the effectiveness of vaccination programs.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».