Real-time tracking of virus evolution

Trevor Bedford (@trvrb)
16 Jul 2018
Weekly Seminar
IDM

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

Outline

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

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

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

Sequenced genomes were representative of spatiotemporal diversity

Phylogenetic reconstruction of epidemic

Tracking migration events

Factors influencing migration rates

Effect of borders on migration rates

Spatial structure at the country level

Substantial mixing at the regional level

Regional outbreaks due to multiple introductions

Zika

Zika's arrival and spread in the Americas

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

Road trip through northeast Brazil to collect samples and sequence

Case reports and diagnostics suggest initiation in northeast Brazil

Phylogeny infers an origin in northeast Brazil

Actionable inferences

Genomic analyses were mostly done in a retrospective manner

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, John Huddleston, Barney Potter,
Emma Hodcroft, Charlton Callender Tom Sibley

Nextstrain architecture

All code open source at github.com/nextstrain

Fauna

Rethink database of virus and titer data

• Harmonizes data from different sources
• Integrates different types of data (serology, sequences, case details)
• Provides an interface for downstream analysis

Augur

Build scripts to align sequences, build trees and annotate

• Flexible build scripts to incorporate different viruses and analyses
• Constructs time-resolved phylogenies
• Annotates with geographic transitions and mutation events

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)

Auspice

Web visualization of resulting trees

• Interactive data exploration and filtering
• Framework through React / D3
• Connects phylogeny, geography and genotypes

nextstrain.org

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

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, Tom Sibley

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, Allison Black, Ester Sabino, Luiz Alcantara

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