Computational Methods for Evaluating Phylogenetic Models of Coding Sequence Evolution with Dependence between Codons
Bibliographic record
Abstract
In recent years, molecular evolutionary models formulated as site-interdependent Markovian codon substitution processes have been proposed as means of mechanistically accounting for selective features over long-range evolutionary scales. Under such models, site interdependencies are reflected in the use of a simplified protein tertiary structure representation and predefined statistical potential, which, along with mutational parameters, mediate nonsynonymous rates of substitution; rates of synonymous events are solely mediated by mutational parameters. Although theoretically attractive, the models are computationally challenging, and the methods used to manipulate them still do not allow for quantitative model evaluations in a multiple-sequence context. Here, we describe Markov chain Monte Carlo computational methodologies for sampling parameters from their posterior distribution under site-interdependent codon substitution models within a phylogenetic context and allowing for Bayesian model assessment and ranking. Specifically, the techniques we expound here can form the basis of posterior predictive checking under these models and can be embedded within thermodynamic integration algorithms for computing Bayes factors. We illustrate the methods using two data sets and find that although current forms of site-interdependent models of codon substitution provide an improved fit, they are outperformed by the extended site-independent versions. Altogether, the methodologies described here should enable a quantified contrasting of alternative ways of modeling structural constraints, or other site-interdependent criteria, and establish if such formulations can match (or supplant) site-independent model extensions.
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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".