Network-based population analysis of 31,595 gonococcal genomes reveals phase variability, genetic diversity and mobile element dynamics drive antimicrobial resistance and phenotypic diversity
Bibliographic record
Abstract
ABSTRACT With a highly plastic genome allowing the accumulation of antimicrobial resistance (AMR) determinants, Neisseria gonorrhoeae ( Ngo ) is an urgent public health threat. To better understand the spread of AMR in Ngo and its ability to persist in humans, we performed a systematic analysis of its global population structure. From 31,595 publicly available genomes, we curated a maximally diverse representative set of 485 gonococcal genomes, which were defined into 12 distinct clades on the basis of shared patterns of single nucleotide polymorphisms. Mapping AMR determinants and mobile elements onto these clades revealed significant correlation with gonococcal population structure. Notably, several variants associated with AMR were identified in genes not previously linked with resistance, suggesting roles as new determinants of resistance or compensatory mutations in resistant strains. Analysis of phase variable motifs, a significant mechanism driving regulation of expression in Ngo , identified 57 genes not previously identified as phase variable; in vivo and in vitro passaging validated our sequence-based definition of phase variability and revealed a strong association of phase variation of the surface proteins Opa and LgtG with improved colonization during infection. Together these findings highlight the ability of systematic comparative genomic analyses to shed new light on the drivers of Ngo population structure and identify new AMR determinants.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".