Key insights from genomic epidemiology
Trevor Bedford
Fred Hutchinson Cancer Center / Howard Hughes Medical Institute
25 Aug 2023
CDC-PGCoE visit
Northwest PGCoE
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
Zika: Uncovering origins of the epidemic in the Americas
Ebola: Revealing spatial spread and persistence in West Africa
MERS: Repeated spillover into the human population from camel reservoir
Actionable inferences
Nextstrain
Project to conduct real-time genomic epidemiology and evolutionary analysis of emerging epidemics
Nextstrain architecture
Central aims: (1) rapid and flexible bioinformatic workflows, (2) interactive visualization and (3) always up-to-date analyses at nextstrain.org
All code open source at github.com/nextstrain
Operationalized during the 2018-2020 outbreak of Ebola in the Democratic Republic of the Congo
Genomic epidemiology during the COVID-19 pandemic
Over 15M SARS-CoV-2 genomes shared to GISAID and evolution tracked in real-time at nextstrain.org
Richard Neher,
Ivan Aksamentov,
Jennifer Chang
James Hadfield,
Emma Hodcroft,
John Huddleston,
Jover Lee,
Victor Lin,
Cornelius Roemer,
Thomas Sibley
Three key insights that genomic epi provided during pandemic
- Rapid human-to-human spread in Wuhan beyond initial market outbreak
- Extensive local transmission while testing was rare
- Identification of variants of concern and mapping of increased transmission rates
Jan 11: First five genomes showed a novel SARS-like coronavirus
Initially thought clustering due to epi investigation of linked cases at Huanan seafood market
Jan 19: First 12 genomes from Wuhan (blue) and Bangkok (red) showed lack of genetic diversity
Jan 23: Introduction into the human population between Nov 15 and Dec 15 and subsequent rapid human-to-human spread
Rapid global epidemic spread from China
Epidemic in the USA was introduced from China in late Jan and from Europe during Feb
Early sequencing provided best estimate of extent of local outbreak
After initial wave, with mitigation
efforts and decreased travel,
regional clades emerge
Emergence of Alpha in the UK with excess spike mutations
Further emergence of variants with increased transmissibility
Variant emergence and spread has continued
In which new variants emerge that escape from existing population immunity and spread rapidly
Future of genomic epidemiology
The COVID-19 pandemic has pushed the field perhaps ~5 years into the future
| 2013-16 Ebola in West Africa | 29k confirmed cases | 1610 genomes |
| 2015-17 Zika in the Americas | 223k confirmed cases | 942 genomes |
| 2018-19 seasonal flu in US | 290k confirmed cases | 8864 genomes |
| 2020-22 COVID-19 pandemic | 732M confirmed cases | 14.5M genomes |
Current research program and work with NW PGCoE
- Continue two major threads
- Evolutionary forecasting: focus on seasonal influenza and SARS-CoV-2 for impact on vaccine strain selection
- Genomic outbreak investigation: across pathogens with focus on spatial dynamics and recontructing spread
- Continue to build out the Nextstrain software platform for broader use by the community
Clade and lineage forecasts continuously updated
Detailed geographic transmission patterns from identical sequences
Lay ground-work for near ubiquitous pathogen sequencing
Acknowledgements
SARS-CoV-2 genomic epi: Data producers from all over the world, GISAID and the Nextstrain team
Bedford Lab:
John Huddleston,
James Hadfield,
Katie Kistler,
Thomas Sibley,
Jover Lee,
Cassia Wagner,
Miguel Paredes,
Nicola Müller,
Marlin Figgins,
Victor Lin,
Jennifer Chang,
Allison Li,
Eslam Abousamra,
Donna Modrell,
Nashwa Ahmed,
Cécile Tran Kiem
