Real-time tracking of RNA viruses using Nextstrain


Richard Neher
Biozentrum & SIB, University of Basel


slides at neherlab.org/202109_Recomb.html

by Trevor Bedford
by Trevor Bedford

Tracking diversity and spread of SARS-CoV-2 in Nextstrain

Available data on Jan 26

Early genomes differed by only a few mutations, suggesting very recent emergence
nextstrain.org/ncov/2020-01-26

>3.5 million sequences

Interactive part on Nextstrain

Tracking variants turned out to be crucial

Emergence and dominance of VoCs

VoCs have more mutations than expected...

nextstrain

VoCs and VoIs: rapid converging evolution

covariants.org by Emma Hodcroft

VoCs have been replacing other strains quickly

S-gene positivity in the UK
Althaus et al, 2021, PHE Technical Briefing

How do we tell early on whether a variant is concerning?

How unusual are the patterns of convergent evolution?

SARS-CoV-2 variants can become dominant without advantage

Hodcroft et al

Spanish EU1 diversity was mirrored across Europe

Hodcroft et al

High case numbers in Spain and high travel volume spread the variant

Hodcroft et al

Travel driven variant dispersal and displacement

  • High invidence differential and high travel volume can shift variant distribution
  • Travel associated activities and behavior further increases impact
  • Onward spread in traveling demographics can be higher

Mutational signatures

Number of amino acid changes in the S1 domain
Prominent deletions the spike NTD
Common convergent deletion in NSP6

Growth measures and experimental scores

Recent growth rate
RBD escape based on deep mutational scanning.
Allie Greaney (Jesse Bloom's lab)

Deep mutational scanning for RBD mutations that affect AB binding and ACE2 binding

Nextclade

  • Within browser alignment and phylgenetic placement
  • Calls mutations relative to the reference
  • Assigns clades
  • Calculates QC metrics

SARS-CoV-2 acknowledgements

  • Emma Hodcroft (now in Bern)
  • Moira Zuber (Basel)
  • Iñaki Comas and Fernando Gonzalez-Candelas, Valencia
  • Martina Reichmuth and Christian Althaus (Bern)
  • Tanja Stadler, Sarah Nadeau, Tim Vaughan at ETH
  • Alberto Hernando and David Matteo at Kido Dynamics
  • Jesse Bloom, Katherine Crawford at Fred Hutch
  • David Veesler, Alex Walls, Davide Corti, John Bowen at UW

Acknowledgments

Trevor Bedford and his lab -- terrific collaboration since 2014

especially James Hadfield, Emma Hodcroft, Ivan Aksamentov, Moira Zuber, John Huddleston, and Tom Sibley

Data we analyze are contributed by scientists from all over the world

Data are shared and curated by GISAID