Real-time genomic surveillance of pathogen evolution and spread


Trevor Bedford (@trvrb)
29 Nov 2017
Epidemics6
Sitges, Spain

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

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 evolution and spread

Dudas et al. 2017. Nature.

Tracking migration events

Dudas et al. 2017. Nature.

Factors influencing 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.

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

Nextstrain architecture

All code open source at github.com/nextstrain

Example augur 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.org

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













Desired analytics are pathogen specific and tied to response measures

Build out pipelines for different pathogens, improve databasing and lower
bioinformatics bar

Acknowledgements


Bedford Lab: Alli Black, Sidney Bell, Gytis Dudas, John Huddleston,
Barney Potter, James Hadfield, Louise Moncla

Ebola: Gytis Dudas, Andrew Rambaut, Luiz Carvalho, Philippe Lemey, Marc Suchard, Andrew Tatem

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