Trevor Bedford (@trvrb)

5 Jun 2017

Global Infectious Disease Seminar

Center for Infectious Disease Research

- Influenza evolution and forecasting
- Ebola spread in West Africa
- Zika spread in the Americas
- "Real-time" analyses

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

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

A simple predictive model estimates the fitness $f$ of virus $i$ as

$$\hat{f}_i = \beta^\mathrm{ep} \, f_i^\mathrm{ep} + \beta^\mathrm{ne} \, f_i^\mathrm{ne}$$

where $f_i^\mathrm{ep}$ measures cross-immunity via substitutions at epitope sites and $f_i^\mathrm{ep}$ measures mutational load via substitutions at non-epitope sites

- Clade frequency change
- Antigenic advancement

*
with Gytis Dudas, Andrew Rambaut, Luiz Carvalho, Marc Suchard, Philippe Lemey,
and many others
*

*
with Nuno Faria, Nick Loman, Oli Pybus, Luiz Alcantara, Ester Sabino, Josh Quick, Allison Black,
Ingra Morales, Julien Thézé, Marcio Nunes, Jacqueline de Jesus, Marta Giovanetti, Moritz Kraemer,
Sarah Hill and many others
*

*
with Nathan Grubaugh, Kristian Andersen, Jason Ladner, Gustavo Palacios, Sharon Isern, Oli Pybus,
Moritz Kraemer, Gytis Dudas, Amanda Tan, Karthik Gangavarapu, Michael Wiley, Stephen White,
Julien Thézé, Scott Michael, Leah Gillis, Pardis Sabeti, and many others
*

*
with Allison Black, Barney Potter, Esther Ellis, Brett Ellis, Kristian Andersen,
Nathan Grubaugh, Leora Feldstein, and others
*

- Timely analysis and sharing of results critical
- Dissemination must be scalable
- Integrate many data sources
- Results must be easily interpretable and queryable

Project to conduct real-time molecular epidemiology and evolutionary analysis of emerging epidemics

Richard Neher,
Trevor Bedford,
James Hadfield,

Colin Megill,
Sidney Bell,
Charlton Callender,

Barney Potter,
Sarah Murata,

All code open source at github.com/nextstrain

**Influenza**: WHO Global Influenza Surveillance Network, GISAID, Worldwide Influenza
Centre at the Francis Crick Institute, Richard Neher, Colin Russell, Boris Shraiman

**Ebola**: Gytis Dudas, Andrew Rambaut, Luiz Carvalho, Philippe Lemey,
Marc Suchard, Andrew Tatem, Nick Loman, Ian Goodfellow, Matt Cotten, Paul Kellam,
Kristian Andersen, Pardis Sabeti, many others

**Zika**: Nick Loman, Nuno Faria, Oliver Pybus, Josh Quick, Kristian Andersen,
Nathan Grubaugh, Jason Ladner, Gustavo Palacios, Sharon Isern, Gytis Dudas, Allison Black, Barney Potter,
Esther Ellis, many others

**Nextstrain**: Richard Neher, James Hadfield, Colin Megill, Sidney Bell,
Charlton Callender, Barney Potter, Sarah Murata