Tracking and interpreting novel SARS-CoV-2 variants
Richard Neher
Biozentrum & SIB, University of Basel
slides at
neherlab.org/202105_ECDC.html
Weekly sequence submissions
Data we analyze are contributed by scientists from all over the world
Data are shared via and curated by GISAID
Nextstrain builds for different countries
nextstrain.org/groups/neherlab
Started as part of the surveillance effort in Switzerland
Most European countries -- updated twice a week
Heavy focus on sequences from the last 4 weeks (but still subsampled in many cases)
Administrative divisions for some countries
Variant specific builds via
CoVariants
We sometimes include experimental features
Moderate effort to add more -- get in touch if you have specific ideas or requests
Similarities to influenza virus evolution
Klingen et al, Trends in MicroBio, 2018
Continuous back and forth between experimental and computational groups.
Challenges assessing novel variants
Frequency dynamics are skewed by sampling biases and varying incidence
Rare sequences might represent large outbreaks in poorly sampled regions
Sudden changes in sampling strategies might look like rapidly increasing frequencies
Focus on specific mutations in known VoCs might miss important others
Laboratory characterization takes time
Prioritization of variants for laboratory characterization.
Harmonized categorization of sequences as
General surveillance
Outbreak investigations
Vaccine breakthroughs, reinfections, etc
Travel associated cases
Support for denser sampling across the globe
(some places in Europe are still undersampled)
Deep mutational scanning for RBD mutations that affect AB binding and ACE2 binding
By Tyler Starr, Allie Greaney, Jesse Bloom and colleagues
Systematic evaluation of all RBD mutations for escape and ACE2 binding
Monoclonals binding to class 1,2,3,4 epitopes
Convalescent and vaccine sera to map population escape
Escape maps of indivual sera and antibodies by Bloom lab
Escape calculator for retained binding by Jesse Bloom
Scoring all sequences for further characterization
Escape in distinct RBD epitope classes
RBD escape in convalescent/vaccine sera
NTD mutations
Other VoC associated mutations (nsp6 del)
ACE2 binding
Furin cleavage site mutations
Recent growth
Incorporation of scores into phylogenetic analysis
Acknowledgments
Trevor Bedford and his lab -- terrific collaboration since 2014
especially James Hadfield, Emma Hodcroft, Ivan Aksamentov, Moira Zuber, and Tom Sibley
Allie Greaney and Jesse Bloom for discussion of the dms data
Data we analyze are contributed by scientists from all over the world
Data are shared and curated by GISAID