SARS-CoV-2 genomics and the growing need for real-time data.

Wisconsin State Laboratory of Hygiene
Kelsey Florek, PhD, MPH
October 15, 2021

Effects of Mutations

• Synonymous Mutation -
  A DNA/RNA mutation that does not change the encoded protein sequence.
• Non-Synonymous Mutation -
  A DNA/RNA mutation that does change the encoded protein sequence, potentially resulting in a change in structure or function.

Comparing non-synonymous mutations to synonymous mutations helps us examine the balance of neutral mutations to beneficial mutations and infer selection.

Positive Selection vs Purifying Selection

• Positive Selection -
  promotes the spread of beneficial alleles; dN/dS > 1
• Purifying Selection -
  hinders the spread of deleterious alleles; dN/dS < 1
• Influenza H3N2 HA -
  example of adaptive viral protein: dN/dS 0.37

Rapid adaptive mutations in Spike protein

What this could mean

Hypothesis 1:
A new selective pressure is acting on SARS-CoV-2 resulting in the appearance of new mutations.

Hypothesis 2:
Mutations have altered the spike protein making it more permissive to additional mutations.

"The potential antigenic impact of adaptive S1 mutations, which are accruing at pace over 4 times that of influenza H3N2, suggests that it may become necessary to update the SARS-CoV-2 vaccine strain given the virus’s demonstrated propensity for adaptive change."

The Takeaways

• Likely in the midst of a global Delta selective sweep.
• The Delta lineage may be following a similar pattern to influenza H1N1pdm with a host adaptation phase followed by a sustained antigenic drift.
• Continued genomic surveillance will be needed to monitor for the emergence of mutations that convey vaccine/antiviral breakthroughs, increased transmission, or increased virulence.

SARS-CoV-2 Surveillance Genomics at WSLH

SARS-CoV-2 Sequencing is a collaborative effort

>1,250 members across Federal Agencies, State and Local Public Health Labs, Academic Institutions, Corporations, and Non-Profit Laboratories

SARS-CoV-2 Sequencing is a collaborative effort

SARS-CoV-2 Cases Sequenced

Sequencing Data Generation

Digesting Complex Data for Public Use

• Phylogenetic trees are useless...
  • How many have we sequenced?
  • Where is the XYZ variant?
  • How many sequences are XYZ variant?
• Near real-time summary data!

Dashboard Data Infrastructure

Dashboard Data Infrastructure

• Uses an accessible data analytics language R.
• Somewhat limited in design and implementation.
• Completely automated!
• Dependent entirely on publicly available data served through 3rd parties.

Building a Genomics Data Warehouse

Central repositories of integrated data from one or more disparate sources used for reporting and data analysis.

Questions?