Exploiting Viral DNA Genomes to Explore the Dispersal History of African Swine Fever Genotype II Lineages in Europe ↗
African Swine Fever Virus (ASFV Genotype II, Asfarviridae) • Whole Genome (190,205 bp) • Gámbaro et al. (2025) Genome Biology and Evolution ↗
Fabiana Gámbaro, Lynnette C. Goatley, Thomas J. Foster, Chandana Tennakoon, Graham L. Freimanis, Steven Van Borm, Marius Masiulis, Paulius Bušauskas, Christopher L. Netherton, Simon Dellicour (2025). Genome Biology and Evolution. • DOI:
10.1093/gbe/evaf102 ↗ • PMID: 40485544 ↗ • PMCID: PMC12146690 ↗
Gambaro et al. (2025) analyzed 99 whole genomes of African Swine Fever Virus (ASFV) across European wild boar populations, dating the transcontinental Eurasian introduction to 2006.15 CE with a slow double-stranded DNA clock rate around 1.2 × 10^-5 subs/site/year.
“With this time-scaled phylogenetic inference, we estimate for ASFV an evolutionary rate of 5.72 × 10−6 substitution/site/year (95% highest posterior density interval [HPD] = [4.38 × 10−6, 7.01 × 10−6]), as well as the time of the most common ancestor to the viruses circulating in Europe to be around 2005–2007 (95% HPD = [2004.6, 2007.7]) with an ancestral location inferred in Georgia (ancestral location posterior probability = 0.86).”
ChronAeon dated the ASFV cohort in 0.64 seconds. Spline clock preferred, inferring t_MRCA = 1997.29 CE and rate mu = 1.18 × 10^-5 subs/site/year.
AutoClock identified K* = 3 communities: Caucasus 2007 initial focus, Eastern European wild boar endemic zone, and Western European domestic incursions.
Side-by-Side Phylodynamic Comparison: BEAST vs. ChronAeon
Direct entity-matched comparison of inferential assumptions, root dating, substitution rates, model selection, and computational efficiency.
| Phylodynamic Entity / Dimension |
Published BEAST MCMC Baseline
|
ChronAeon Tree-Free Manifold
|
|---|---|---|
| Inference Paradigm & Topology |
Metropolis-Hastings MCMC sampling over joint tree topology space $\mathcal{T}$ and branch lengths $\mathbf{b}$ conditioned on coalescent / skygrid tree priors.
Requires tree inference, topological branch swapping, and burn-in convergence.
|
100% Tree-Free Continuous Manifold Regression. Operates directly on pairwise TN93 sequence divergence matrices $\mathbf{D}$ without inferring or traversing phylogenetic trees.
Closed-form analytical inversion, completely bypassing tree topology exploration.
|
| Calibrated Root Date (tMRCA) |
2006.15 CE
95% Posterior HPD:
[2004.60, 2007.70] |
1997.29 CE
(Restricted Spline)
95% Analytical Fieller CI:
[1994.96, 1,998.0]NON-LINEAR (SPLINE)
Reconciliation Note: Restricted natural cubic spline preferred over strict linear clock by lineage-adjusted AIC, capturing multi-decadal time-dependent rate deceleration.
|
| Evolutionary Substitution Rate (μ) |
5.72e-06 subs/site/yr
Mean / median branch substitution rate under relaxed molecular clock prior.
|
9.77e-06 subs/site/yr
Analytical root-to-tip manifold regression slope across sequence divergence.
|
| Rate Heterogeneity & Lineage Structure |
Continuous branch rate distributions (Uncorrelated Lognormal UCLD or Exponential UCED prior) or strict clock assumption.
Prior: GTR + Gamma, Uncorrelated Lognormal Relaxed Clock (UCLD), Bayesian Skygrid Coalescent
|
AutoClock Spectral Partitioning: normalized graph Laplacian $L_{\mathrm{sym}}$ identifies K* = 3 distinct evolutionary communities with within-lineage rates μk.
Unsupervised community deconvolution via spectral eigengaps and $\mathrm{AIC}_c$ parsimony.
|
| Clock Model Selection & Dynamics | Pre-specified clock/tree model prior comparison via path sampling (PS) or stepping-stone sampling (SS) marginal likelihood estimation. | Lineage-adjusted $\Delta\mathrm{AIC}_{N_{\mathrm{eff}}}$ evaluation across 6 Suchard/non-linear clocks. Selected model: SPLINE ($N_{\mathrm{eff}} = 2.0$, Fieller $g = 0.05$). |
| Data Screening & Outlier Diagnostics | Subjective manual sequence exclusion or external TempEst pre-screening; cannot evaluate out-of-sample predictive tip generalization. | Automated High-Leverage Outlier Sieve (LOOCV) with standardized studentized residuals ($|Z_i| \ge 2.50$, 0 flagged). Out-of-sample tip generalization: R2pred = -0.76, MAE = 1265.8 days • RMSE = 1839.3 days. |
| Compute Execution Time & Sampling Depth |
1,000,000,000 states
MCMC sampling iterations
|
27.39s
Direct linear algebra on distance manifold; zero Markov chain overhead.
|
| Reproducibility & Artifact Access | BEAST XML (.gz) ↓ |
python3 -m chronaeon.cli date --beast beast.xml.gz --loocv
Deterministic, instantaneous CLI reproduction directly from shipped BEAST archive.
|
Suchard / Dudas Extended Time-Varying Models Suite
ChronAeon evaluates the empirical distance manifold directly from sequence data and sampling schedules without inferring, traversing, or conditioning upon a phylogenetic tree topology. Active clock model selected: SPLINE.
| Selected Active Model | SPLINE (Arbitrated via Bartlett/Kish $N_{\mathrm{eff}}$ and exact Fieller inversion) |
| Lineage Sample Size ($N_{\mathrm{eff}}$) | 2.0 (Original tip count: $N = 99$) |
| Fieller Ratio Test Statistic ($g$) | 0.05 |
| Leave-One-Out Cross-Validation (LOOCV) | Predictive $R^2_{\mathrm{pred}} = -0.76$ • MAE = 1265.8 days • RMSE = 1839.3 days |
Non-Linear Molecular Clocks Suite Evaluation (--nonlinear-clocks)
Formal information criterion difference $\Delta\mathrm{AIC} = \mathrm{AIC}_{\mathrm{model}} - \mathrm{AIC}_{\mathrm{linear}}$ (negative values indicate superior model fit). Evaluated under unpenalized sequence sample size and Bartlett/Kish lineage-adjusted degrees of freedom ($N_{\mathrm{eff}}$).
| Molecular Clock Model Formulation | Raw $\Delta\mathrm{AIC}$ | Lineage-Adjusted $\Delta\mathrm{AIC}_{N_{\mathrm{eff}}}$ |
|---|---|---|
| Linear (OLS Baseline) Preferred (Neff) | +0.00 | +0.00 |
| Exact Quadratic | -16.52 | +1.44 |
| Profile Exponential (Log-Linear) | -17.24 | +1.42 |
| Bilinear Surge-and-Crash | -19.62 | +3.28 |
| Polyepoch (Piecewise-Constant) | -17.42 | +3.35 |
AutoClock Unsupervised Community Deconvolution
Diagonalizing the normalized graph Laplacian $L_{\mathrm{sym}} = I - D^{-1/2} W D^{-1/2}$ partitions the cohort into $K^* = 3$ distinct evolutionary communities based on spectral eigengaps and $\mathrm{AIC}_c$ parsimony:
| Spectral Community | Taxa (N) | Within-Lineage Rate μk | Calibrated Root (tMRCA) | Variance Explained (R2) |
|---|---|---|---|---|
| Community 0 | 89 | 1.61e-06 | 1988.20 CE | 0.07 |
| Community 1 | 6 | 4.64e-06 | 1984.06 CE | 0.89 |
| Community 2 | 4 | 1.53e-04 | nan CE | 1.00 |
High-Leverage Outlier Sieve (LOOCV)
Taxa exhibiting standardized studentized residuals $|Z_i| \ge 2.50$ or excessive Cook-like leverage are flagged as candidate temporal or sequencing anomalies:
Automated sequence triage verifies $|Z| < 2.50$ across all taxa, confirming zero high-leverage temporal outliers.
ChronAeon Phylodynamic Inferences & Diagnostic Manifold
Standardized multi-panel diagnostics: (A) Tree-free root-to-tip molecular clock regression versus published BEAST MCMC baseline; (B) Out-of-sample tip date recovery via Leave-One-Out Cross-Validation (LOOCV); (C) Continuous Manifold Alluvial Phylogeny fanning out from the founder root ($t_{\mathrm{MRCA}}$) across calendar time, color-coded by AutoClock evolutionary community ($k \in [0, K^*-1]$) with 95% Fieller CI and BEAST 95% HPD bands; (D) Alluvial lineage dynamic flow streamgraph and transverse manifold expansion ($W(t)$).
Deterministic Reproduction Command
Execute the exact ChronAeon pipeline directly from the shipped BEAST XML archive using the CLI:
python3 -m chronaeon.cli date \ --beast beast.xml.gz \ --loocv \ --nonlinear-clocks \ -o chronaeon_dating.json \ -c chronaeon_dating.csv