Trevor Bedford (@trvrb)

23 Apr 2018

HIV Dynamics and Evolution

Leavenworth, WA

- "These observations have implications for influenza surveillance and vaccine formulation" (Wolf et al 2006)
- "Our results have implications for the design of vaccines to combat rapidly mutating viral diseases" (Gupta et al 2006)
- "These results may have important implications for influenza vaccine and antiviral research" (Bhatt et al 2011)
- "Needless to say, these results have important implications for the updating of vaccines against influenza" (Zinder et al 2013)

- WHO needs
*specific*advice, ie this strain is likely to take off, this strain is likely to die out - Problems of generality and timeliness

- Charts behavior of specific strains
- Can be kept continually up to date

Project to provide a real-time view of the evolving influenza population

Project to provide a real-time view of the evolving influenza population

All in collaboration with Richard Neher

- Download all recent HA sequences from GISAID
- Filter to remove outliers
- Subsample across time and space
- Align sequences
- Build tree
- Estimate clade frequencies
- Infer antigenic phenotypes
- Export for visualization

*
with
Richard Neher,
James Hadfield,
Colin Megill,
Sidney Bell,
John Huddleston,
Barney Potter,
Charlton Callender,
Emma Hodcroft
*

"The future is here, it's just not evenly distributed yet"

— William Gibson

Clade frequencies $X$ derive from the fitnesses $f$ and frequencies $x$ of constituent viruses, such that

$$\hat{X}_v(t+\Delta t) = \sum_{i:v} x_i(t) \, \mathrm{exp}(f_i \, \Delta t)$$

This captures clonal interference between competing lineages

- Amino acid changes at epitope sites
- Antigenic novelty based on HI
- Rapid phylogenetic growth

where the fitness $f$ of virus $i$ is estimated as

$$\hat{f}_i = \beta^\mathrm{HI} \, f_i^\mathrm{HI} + \beta^\mathrm{freq} \, f_i^\mathrm{freq}$$

where $f_i^\mathrm{HI}$ measures antigenic drift via HI and $f_i^\mathrm{freq}$ measures clade growth/decline

We learn coefficients and validate model based on previous 15 H3N2 seasons

- Systematically test fitness predictors
- Include geographic component to fitness model
- Incorporate information from other segments
- Integrate human serology to estimate selective landscape

**Bedford Lab**:
Alli Black,
Sidney Bell,
Gytis Dudas,
John Huddleston,

Barney Potter,
James Hadfield,
Louise Moncla

**Influenza**: WHO Global Influenza Surveillance Network, GISAID, Richard Neher,
Barney Potter, John Huddleston, James Hadfield, Colin Russell, Andrew Rambaut, Dave Wentworth, Becky Garten, Jackie Katz,
Marta Łuksza, Michael Lässig, Richard Reeve

**Nextstrain**: Richard Neher, James Hadfield, Colin Megill, Sidney Bell,
Charlton Callender, Barney Potter, John Huddleston, Emma Hodcroft