Real-time tracking of virus evolution


 

Trevor Bedford (@trvrb)
7 May 2019
Northwest Data Science Summit
University of Washington
 
Slides at: bedford.io/talks

Spread of plague in 14th century

Spread of swine flu in 2009

Sequencing to reconstruct pathogen spread

Epidemic process

Sample some individuals

Sequence and determine phylogeny

Sequence and determine phylogeny

Phylogenetic tracking has the capacity to revolutionize epidemiology

Pathogen genomes may reveal:

  • Evolution of new adaptive variants
  • Epidemic origins
  • Patterns of geographic spread
  • Animal-to-human spillover
  • Transmission chains

Influenza: Forecasting spread of new variants for vaccine strain selection

Bedford and Neher. 2018. bioRxiv.

Zika: Uncovering origins of the epidemic in the Americas

Faria et al. 2017. Nature.

Ebola: Revealing spatial spread and persistence in West Africa

Dudas et al. 2017. Nature.

Ebola: Revealing spatial spread and persistence in West Africa

Dudas et al. 2017. Nature.

Ebola: Revealing spatial spread and persistence in West Africa

Dudas 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,
John Huddleston, Colin Megill, Sidney Bell, Barney Potter,
Charlton Callender

Nextstrain architecture

All code open source at github.com/nextstrain

Two central aims: (1) rapid and flexible phylodynamic analysis and
(2) interactive visualization

Rapid build pipeline for 1600 Ebola genomes

  • Align with MAFFT (34 min)
  • Build ML tree with RAxML (54 min)
  • Temporally resolve tree and geographic ancestry with TreeTime (16 min)
  • Total pipeline (1 hr 46 min)

Nextstrain is two things

  • a bioinformatics toolkit and visualization app, which can be used for a broad range of datasets
  • a collection of real-time pathogen analyses kept up-to-date on the website nextstrain.org

nextstrain.org

Rapid on-the-ground sequencing in Makeni, Sierra Leone













Newly released features

  • Bacteria build pipelines using VCF rather than FASTA
  • "Community" builds to promote frictionless sharing of results

Genomic epidemiology of the ongoing DRC Ebola epidemic

INRB/USAMRIID Nextstrain
               

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

Genomic epi: Richard Neher, Gytis Dudas, Andrew Rambaut, Luiz Carvalho, Nick Loman, Nuno Faria, Oli Pybus, Josh Quick, Matt Cotten, Ian Goodfellow, Alli Black, Louise Moncla, John Huddleston

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

Seattle Flu Study: Helen Chu, Michael Boeckh, Janet Englund, Michael Famulare, Barry Lutz, Debbie Nickerson, Mark Rieder, Lea Starita, Matthew Thompson, Jay Shendure, Jeris Bosua, Thomas Sibley, Louise Moncla, Barney Potter, Jover Lee, Kairsten Fay, Misja Ilcisin, James Hadfield, Antonio Solano