### Human seasonal influenza viruses

slide by Trevor Bedford
- Influenza virus evolves to avoid human immunity
- Vaccines need frequent updates

## Beyond tracking: can we predict?

### Clonal interference and traveling waves

RN, Annual Reviews, 2013; Desai & Fisher; Brunet & Derrida; Kessler & Levine
### Predicting evolution

### Given the branching pattern:

- can we predict fitness?
- pick the closest relative of the future?

RN, Russell, Shraiman, eLife, 2014
### Fitness inference from trees

$$P(\mathbf{x}|T) = \frac{1}{Z(T)} p_0(x_0) \prod_{i=0}^{n_{int}} g(x_{i_1}, t_{i_1}| x_i, t_i)g(x_{i_2}, t_{i_2}| x_i, t_i)$$

RN, Russell, Shraiman, eLife, 2014
### Prediction of the dominating H3N2 influenza strain

- no influenza specific input
- how can the model be improved? (see model by Luksza & Laessig)
- what other context might this apply?

RN, Russell, Shraiman, eLife, 2014
### Hemagglutination Inhibition assays

Slide by Trevor Bedford
### HI data sets

- Long list of distances between sera and viruses
- Tables are sparse, only close by pairs
- Structure of space is not immediately clear
- MDS in 2 or 3 dimensions

Smith et al, Science 2002
Slide by Trevor Bedford
### Integrating antigenic and molecular evolution

- $H_{a\beta} = v_a + p_\beta + \sum_{i\in (a,b)} d_i$
- each branch contributes $d_i$ to antigenic distance
- sparse solution for $d_i$ through $l_1$ regularization
- related model where $d_i$ are associated with substitutions

RN et al, PNAS, 2016
### HI distances on the phylogenetic tree

## Summary

- RNA virus evolution can be observed directly
- Rapidly adapting population require new population genetic models
- Those model can be used to infer fit clades
- Future influenza population can be anticipated
- Automated real-time analysis can help fight the spread of disease

### Influenza and Theory acknowledgments

- Boris Shraiman
- Colin Russell
- Trevor Bedford
- Oskar Hallatschek

### nextstrain.org

- Trevor Bedford
- Colin Megill
- Pavel Sagulenko
- Sidney Bell
- James Hadfield
- Wei Ding