Real-time tracking of virus evolution



 

Trevor Bedford (@trvrb)

We work at the interface of virology, evolution and epidemiology

Segue through data vizualization

Data tells a story

Charles Minard and Napoleon's 1812 campaign

If data are looked at in the right way, answers become immediately clear

Edward Tufte

Above all, show the data

A good graphic is honest

Barchart of average value

Box-and-whisker plot showing variation

Showing the data

To clarify add detail

"To clarify, add detail... Clutter and overload are not attributes of information, they are failures of design. If the information is in chaos, don’t start throwing out information, instead fix the design."
– Tufte

Evolution of Conus shells

Gong et al. 2012

Greenland rising

Bevis et al. 2012

Small multiples and dimensionality

Mapping infection spread

John Snow and the founding of epidemiology

Global pandemic spread

Brockmann et al. 2013

Geographic distance does not describe pandemic spread

Brockmann et al. 2013

Shortest network path captures pandemic spread

Brockmann et al. 2013

My research

Methods focus on sequencing to reconstruct pathogen spread

Epidemic process

Sample some individuals

Sequence and determine phylogeny

Sequence and determine phylogeny

Localized Middle Eastern MERS-CoV phylogeny

Cotten et al. 2013. Lancet.

Regional West African Ebola phylogeny

Park et al. 2015. Cell.

Global influenza phylogeny

Bedford et al. 2015. Nature.

Phylogenetic tracking has the capacity to revolutionize epidemiology

Outline

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

Influenza

Dynamics driven by antigenic drift

Drift variants emerge and rapidly take over in the virus population


This causes the side effect of evading existing vaccine formulations

Drift necessitates vaccine updates

We're trying to forecast which strains will take over in the coming year and inform vaccine strain selection

Some present-day clades contribute disproporiately to the future population

Huddleston et al. 2019. Unpublished.

Ebola

Virus genomes reveal factors that spread and sustained the Ebola epidemic

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

Dudas et al. 2017. Nature.

Sequencing of 1610 Ebola virus genomes collected during the 2013-2016 West African epidemic

Dudas et al. 2017. Nature.

Phylogenetic reconstruction of epidemic

Dudas et al. 2017. Nature.

Initial emergence from Guéckédou

Dudas et al. 2017. Nature.

Tracking migration events

Dudas et al. 2017. Nature.

Factors influencing migration rates

Dudas et al. 2017. Nature.

Effect of borders on migration rates

Dudas et al. 2017. Nature.

Spatial structure at the country level

Dudas et al. 2017. Nature.

Substantial mixing at the regional level

Dudas et al. 2017. Nature.

Regional outbreaks due to multiple introductions

Dudas et al. 2017. Nature.

Zika

Zika's arrival and spread in the Americas

WHO 2016

Establishment and cryptic transmission of Zika virus in Brazil and the Americas

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

Faria et al. 2017. Nature.

Road trip through northeast Brazil to collect samples and sequence

Faria et al. 2017. Nature.

Case reports and diagnostics suggest initiation in northeast Brazil

Faria et al. 2017. Nature.

Phylogeny infers an origin in northeast Brazil

Faria et al. 2017. Nature.

Actionable inferences

Genomic analyses were mostly done in a retrospective manner

Dudas and Rambaut 2016

Key challenges to making genomic epidemiology actionable

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

Nextstrain

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


with Richard Neher, James Hadfield, Emma Hodcroft, Thomas Sibley, Colin Megill, John Huddleston, Barney Potter, Sidney Bell, Louise Moncla, Charlton Callender, Misja Ilcisin, Kairsten Fay, Jover Lee

Nextstrain architecture

All code open source at github.com/nextstrain

nextstrain.org

Rapid on-the-ground sequencing by Ian Goodfellow, Matt Cotten and colleagues













Lab directions

  • Outbreak investigations (mumps in Washington, Zika in Colombia, etc...)
  • Phylodynamics methods development
  • Evolutionary forecasting methods development
  • Software infrastructure for Nextstrain and genomic epidemiology

Acknowledgements

Bedford Lab: Alli Black, John Huddleston, Barney Potter, James Hadfield,
Katie Kistler, Louise Moncla, Maya Lewinsohn, Thomas Sibley,
Jover Lee, Kairsten Fay, Misja Ilcisin

Influenza: WHO Global Influenza Surveillance Network, GISAID, Richard Neher, John Huddleston, Barney Potter, Dave Wentworth, Becky Kondor   Ebola: Gytis Dudas, Andrew Rambaut, Luiz Carvalho, Philippe Lemey, Marc Suchard, Andrew Tatem   Zika: Nick Loman, Nuno Faria, Oli Pybus, Josh Quick, Ingra Claro, Julien Thézé, Jaquilene de Jesus, Marta Giovanetti, Moritz Kraemer, Sarah Hill, Ester Sabino, Luiz Alcantara, Allison Black   Nextstrain: Richard Neher, James Hadfield, Emma Hodcroft, Thomas Sibley, John Huddleston, Sidney Bell, Barney Potter, Colin Megill, Charlton Callender