Bayesian phylodynamics of HBV and SARS-CoV-2
Barney Isaksen Potter
KU Leuven
2024-02-12
Grubaugh Lab Meeting, Yale School of Public Health
What can phylogenetics tell us?
- Phylogeny
- Evolutionary rate
- Substitution rates
- Demographic parameters
- Migration rates
- Migration history
What can phylogenetics tell us?
- Phylogeny
- Evolutionary rate
- Substitution rates
- Demographic parameters
- Migration rates
- Migration history
What can phylogenetics tell us?
- Phylogeny
- Evolutionary rate
- Substitution rates
- Demographic parameters
- Migration rates
- Migration history
\[\tiny
Q_{JC69} =
\begin{bmatrix}
\cdot & \lambda & \lambda & \lambda \\
\lambda & \cdot & \lambda & \lambda \\
\lambda & \lambda & \cdot & \lambda \\
\lambda & \lambda & \lambda & \cdot \\
\end{bmatrix} \\[1em]
Q_{GTR} =
\begin{bmatrix}
\cdot & a\pi_C & b\pi_A & c\pi_G \\
a\pi_T & \cdot & d\pi_A & e\pi_G \\
b\pi_T & d\pi_C & \cdot & f\pi_G \\
c\pi_T & e\pi_C & f\pi_A & \cdot \\
\end{bmatrix}
\]
What can phylogenetics tell us?
- Phylogeny
- Evolutionary rate
- Substitution rates
- Demographic parameters
- Migration rates
- Migration history
What can phylogenetics tell us?
- Phylogeny
- Evolutionary rate
- Substitution rates
- Demographic parameters
- Migration rates
- Migration history
What can phylogenetics tell us?
- Phylogeny
- Evolutionary rate
- Substitution rates
- Demographic parameters
- Migration rates
- Migration history
How can we infer phylogenies robustly from genomic sequence data and geographic metadata?
Problem: parameter space size
\[\tiny
\begin{array}{cc}
Num.~taxa & Num.~topologies \\ \hline
1 & 1 \\
2 & 1 \\
3 & 3 \\
4 & 15 \\
5 & 105 \\
6 & 945 \\
7 & 10,395 \\
8 & 135,135 \\
9 & 2,027,025 \\
\vdots & \vdots \\
769 & 3.753 \times 10^{2,110} \\
\end{array}
\]
Source: Stamatakis & Kozlov (2020)
Enter: Bayes' Theorem
\[
P(\theta|\textbf{D}) = \frac{P(\textbf{D} |\theta) \times P(\theta )}{P(\textbf{D})}
\]
Source: Jin, Ju, & Jung (2019)
Hepatitis B Phylogeography
Source: CDC/ Dr. Erskine Palmer
What is HBV?
- Causative agent of hepatitis B
- Cirrhosis
- Hepatocellular carcinoma
- Spread through blood and bodily fluids
- Affects $\geq 350,000,000$ people annually
- Partially dsDNA genome
- Long strand: 3 kb
- Short strand: 2.2 kb
Source: Wikimedia Commons
Source: Morens & Fauci (2020)
Source: Kocher et al. (2021)
Source: Shi et al. (2013)
Our study
- 133 HBV positive individuals who have recently immigrated from sub-Saharan Africa
- 118 full genome sequences:
- 47 HBV-A;
- 7 HBV-D;
- 64 HBV-E.
- Supplemented with all available high quality GenBank HBV genomes
Reconstruct evolutionary and migration history of three HBV genotypes (A, D, E):
- Identify subgenotypes for novel sequences (A/D);
- Date the most recent common ancestor of each genotype;
- Characterize number and timing of major viral migrations.
Sampling bias complicates phyogeographic inference
Source: Mülemann et al. (2018)
\[\scriptsize
\begin{array}{cccc}
\textbf{Sequence} & \textbf{Genotype} & \textbf{Location} & \textbf{Age~(year)} \\ \hline
\textrm{Rise386} & \textrm{HBV-A} & \textrm{Russia}^* & 4,114 \textrm{(2100 BCE)} \\
\textrm{Rise387} & \textrm{HBV-A} & \textrm{Russia}^* & 4,278 \textrm{(2264 BCE)} \\
\textrm{DA119} & \textrm{HBV-A} & \textrm{Slovakia} & 1,563 \textrm{(451 CE)} \\
\textrm{DA195} & \textrm{HBV-A} & \textrm{Hungary} & 2,641 \textrm{(627 BCE)} \\ \hline
\textrm{DA27} & \textrm{HBV-D} & \textrm{Kazakhstan} & 1,610 \textrm{(409 CE)} \\
\textrm{DA29} & \textrm{HBV-D} & \textrm{Kazakhstan} & 822 \textrm{(1197 CE)} \\
\textrm{DA51} & \textrm{HBV-D} & \textrm{Kyrgyzstan} & 2,297 \textrm{(278 BCE)} \\
\textrm{DA222} & \textrm{HBV-D} & \textrm{Kazakhstan} & 1,167 \textrm{(852 CE)} \\
\textrm{NASD24SEQ} & \textrm{HBV-D} & \textrm{Italy} & 427 \textrm{(1587 CE)}
\end{array}
\]
Clock rate prior: $1.18 \times 10^{-5}$ [95% HPD: $8.04 \times 10^{-6} \textrm{--} 1.51 \times 10^{-5}$] subs./site/year
Source: Mülemann et al. (2018), Ross et al. (2018)
Takeaways and next steps
- Large-scale human movements drives HBV globalization.
- More global genomic surveillance of HBV is necessary to understand the diversity and potential impact of each genotype.
- Ancient genomes may refine inferences of future HBV datasets.
BA.1 Phylogeography in Pakistan
- 1690 global Omicron (BA.1) genomes
- 63 from Pakistan
- 15 with travel-histories
- 32 discrete geographic areas
- Pakistan and neighboring countries
- Regions of China
- UN Geogregions
- Roughly one third of Pakistan's fifth wave
Source: Layan et al (2023)
Source: Lemey et al (2020)
WARNING: bad looking WIP figures ahead
ECV-KU Leuven
- Guy Baele
- Mandev Gill
- Philippe Lemey
- Samuel Hong
Fogarty International Center
Vilnius University
Rega Institute
- Mahmoud Reza Pourkarim
- Marijn Thijssen
NIH Pakistan
- Massab Umair
- Zaira Rehman
- Aamer Ikram
- Muhammad Salman
Belgian American Education Foundation
