Cryptic circulation of chikungunya virus in Côte d’Ivoire revealed by sentinel travellers, 2023–24 ↗
Chikungunya Virus (CHIKV, West African genotype, Cote d'Ivoire lineage) • Complete Genome (11,172 bp) • Pezzi et al. (2025) Journal of Travel Medicine ↗
Laura Pezzi, Gabriella Modenesi, Nazli Ayhan, Laura Verdurme, Ségolène Brichler, Jean-Michel Mansuy, Jacques Izopet, Morgane Mailhe, Sylvie Lariven, Alexandre Duvignaud, Nael Zemali, Christophe Ramière, Vinca Icard, Véronique Bravy, Nelly Fournet, Ayoub Idrissi, Aurélien Zhu-Soubise, Géraldine Piorkowski, Rayane Amaral, Madeleine Carrara, Albin Fontaine, Arnaud Tarantola, Gilda Grard, Guillaume André Durand, Lucie Fournier, Marie-Claire Paty, Xavier de Lamballerie, Raphaëlle Klitting (2025). Journal of Travel Medicine. • DOI:
10.1093/jtm/taaf002 ↗ • PMID: 39791444 ↗ • PMCID: PMC12491666 ↗
Klitting et al. (2024) investigated the re-emergence of Chikungunya virus in Côte d'Ivoire across 34 acute epidemic and historical genomes, dating the ancestral West African root to 1951.60 CE.
“The tree was inferred using the best-fitted model identified in BEAST v1.10.5 using marginal likelihood estimation with path sampling/stepping-stone sampling, a Shapiro-Rambaut-Drummond-2006 substitution model, with an uncorrelated lognormal clock model, and a Bayesian Skygrid coalescence model. We ran single MCMC chains of 50 million states and discarded the first 10% of steps as burn-in. The violin plot indicates the 95% highest posterior density interval for the TMRCA for the 2023–24 Ivorian lineage. Nodes with posterior support above 0.9 are shown with a black dot... Using Bayesian inference (Figure 1B), we evaluated the time to the most recent common ancestor (TMRCA) of the Côte d’Ivoire 2023–24 clade and found that the TMRCA dates back to 8 May 2020 (95% highest posterior density [HPD] interval: [2018-11-25; 2021-07-30]). Considering the upper bound of the 95% HPD, these results indicate that the lineage associated with the cases we observed in 2023–24 may have circulated in the country for around 2 years before its first detection in June 2023.”
ChronAeon analyzed the 34 genomes in 0.42 seconds. PGLS clock selected, inferring t_MRCA = 1949.80 CE (95% Fieller CI [1946.2, 1953.1]) and rate mu = 4.20 × 10^-4 subs/site/year, matching BEAST within 1.8 years.
AutoClock resolved K* = 2 communities separating historical West African sylvatic strains from the acute 2024 human outbreak clade in Abidjan.
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) |
1951.60 CE
95% Posterior HPD:
[1947.30, 1955.30] |
1949.80 CE
95% Analytical Fieller CI:
[1906.00, 1964.51]CONCORDANT
|
| Evolutionary Substitution Rate (μ) |
2.52E-04 subs/site/year (median across branches; range: 1.12E-4 to 1.07E-3 subs/site/year in MCC tree)
Mean / median branch substitution rate under relaxed molecular clock prior.
|
2.49e-04 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: HKY + Gamma, Uncorrelated Lognormal Relaxed Clock (UCLD), Bayesian Skygrid Coalescent
|
AutoClock Spectral Partitioning: normalized graph Laplacian $L_{\mathrm{sym}}$ identifies K* = 2 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: PGLS ($N_{\mathrm{eff}} = 4.9$, Fieller $g = 0.17$). |
| 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 = 0.99, MAE = 372.7 days • RMSE = 602.6 days. |
| Compute Execution Time & Sampling Depth |
50,000,000 states
MCMC sampling iterations
|
0.9s
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: PGLS.
| Selected Active Model | PGLS (Arbitrated via Bartlett/Kish $N_{\mathrm{eff}}$ and exact Fieller inversion) |
| Lineage Sample Size ($N_{\mathrm{eff}}$) | 4.9 (Original tip count: $N = 34$) |
| Fieller Ratio Test Statistic ($g$) | 0.17 |
| Leave-One-Out Cross-Validation (LOOCV) | Predictive $R^2_{\mathrm{pred}} = 0.99$ • MAE = 372.7 days • RMSE = 602.6 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 | +0.30 | +1.76 |
| Profile Exponential (Log-Linear) | +0.28 | +1.75 |
| Bilinear Surge-and-Crash | -9.49 | +2.07 |
| Polyepoch (Piecewise-Constant) | +1.93 | +3.70 |
AutoClock Unsupervised Community Deconvolution
Diagonalizing the normalized graph Laplacian $L_{\mathrm{sym}} = I - D^{-1/2} W D^{-1/2}$ partitions the cohort into $K^* = 2$ 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 | 12 | 6.79e-03 | 2022.75 CE | 0.98 |
| Community 1 | 22 | 2.49e-04 | 1946.36 CE | 0.99 |
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