Detecting amino acid preference shifts with codon-level mutation-selection mixture models
Bibliographic record
Abstract
BACKGROUND: In recent years, increasing attention has been placed on the development of phylogeny-based statistical methodologies for uncovering site-specific changes in amino acid fitness profiles over time. The few available random-effects approaches, modelling across-site variation in amino acid profiles as random variables drawn from a statistical law, either lack a mechanistic codon-level formulation, or pose significant computational challenges. RESULTS: Here, we bring together a few existing ideas to explore a simple and fast method based on a predefined finite mixture of amino acid profiles within a codon-level substitution model following the mutation-selection formulation. Our study is focused on the detection of site-specific shifts in amino acid profiles over a known sub-clade of a tree, using simulations with and without shifts over the sub-clade to study the properties of the method. Through modifications of the values of the amino acid profiles, our simulations show different levels of reliability under different forms of finite mixture models. Sites identified by our method in a real data set show obvious overlap with those identified using previous methods, with some notable differences. CONCLUSION: Overall, our results show that when a site-specific shift in amino acid profile is strongly pronounced, involving two clearly different sets of profiles, the method performs very well; but shifts between profiles that share many features are difficult to correctly identify, highlighting the challenging nature of the problem.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".