A model-based clustering method to detect infectious disease transmission outbreaks from sequence variation
Bibliographic record
Abstract
Clustering infections by genetic similarity is a popular technique for identifying potential outbreaks of infectious disease, in part because sequences are now routinely collected for clinical management of many infections. A diverse number of nonparametric clustering methods have been developed for this purpose. These methods are generally intuitive, rapid to compute, and readily scale with large data sets. However, we have found that nonparametric clustering methods can be biased towards identifying clusters of diagnosis-where individuals are sampled sooner post-infection-rather than the clusters of rapid transmission that are meant to be potential foci for public health efforts. We develop a fundamentally new approach to genetic clustering based on fitting a Markov-modulated Poisson process (MMPP), which represents the evolution of transmission rates along the tree relating different infections. We evaluated this model-based method alongside five nonparametric clustering methods using both simulated and actual HIV sequence data sets. For simulated clusters of rapid transmission, the MMPP clustering method obtained higher mean sensitivity (85%) and specificity (91%) than the nonparametric methods. When we applied these clustering methods to published sequences from a study of HIV-1 genetic clusters in Seattle, USA, we found that the MMPP method categorized about half (46%) as many individuals to clusters compared to the other methods. Furthermore, the mean internal branch lengths that approximate transmission rates were significantly shorter in clusters extracted using MMPP, but not by other methods. We determined that the computing time for the MMPP method scaled linearly with the size of trees, requiring about 30 seconds for a tree of 1,000 tips and about 20 minutes for 50,000 tips on a single computer. This new approach to genetic clustering has significant implications for the application of pathogen sequence analysis to public health, where it is critical to robustly and accurately identify clusters for the most cost-effective deployment of outbreak management and prevention resources.
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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 | 0.003 | 0.010 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".