Phylodynamics introduction

Trevor Bedford (@trvrb)
May 26, 2020
GS541 Introduction to Computational Molecular Biology

SARS-CoV-2

epiforecasts.io

Significant fog of war. Genomic approaches offer orthogonal data source to understand the pandemic.

Epidemic process

Sample some individuals

Sequence and determine phylogeny

Sequence and determine phylogeny

Nextstrain

Project to conduct real-time molecular epidemiology and evolutionary analysis of emerging epidemics

Nextstrain architecture

All code open source at github.com/nextstrain

Two central aims: (1) rapid and flexible phylodynamic analysis and
(2) interactive visualization

Rapid build pipeline for 3000 SARS-CoV-2 genomes (timings are for a laptop)

Align with MAFFT (~20 min)
Build ML tree with IQTREE (~40 min)
Temporally resolve tree and geographic ancestry with TreeTime (~50 min)
Total pipeline (~2 hr)

Flexible pipelines constructed through command line modules

Modules called via augur filter, augur tree, augur traits, etc...
Designed to be composable across pathogen builds
Defined pipeline, making steps obvious
Provides dependency graph for fast recomputation
Pathogen-specific repos give users an obvious foundation to build from
SARS-CoV-2 workflow here

Current data flow for SARS-CoV-2

Labs contribute directly to GISAID (now have >17k full genomes)
Nextstrain pulls a complete dataset from GISAID every 60 minutes
This triggers an automatic rebuild on Amazon Web Services
We manually update new lat/longs, etc...
We push this build online to nextstrain.org and tweet the update from @nextstrain

We do about one update per 12 hours via Seattle and Basel. We were regularly getting 200k visitors per day to the site, now down to 50k.

Dec/Jan: Emergence of SARS-CoV-2 from Wuhan in ~Nov 2019

Jan/Feb: Spread within China and seeding elsewhere

Feb/Mar: Epidemic spread within North America and Europe

Mar/Apr: Continued growth, but decreasing transmission with social distancing measures

Epidemic in the USA was introduced from China in late Jan and from Europe during Feb

Once in the US, virus spread rapidly

Single introduction ~Feb 1 quickly shows up throughout the country

States show different patterns

States show different patterns

States show different patterns

States show different patterns

States show different patterns

States show different patterns

Dive into phylogeny

Generally, phylodynamic inference allows us to:

Infer changes in population size, ie prevalence, through time
Infer spatial movements of the epidemic and patterns of seeding
Infer differences in transmission rates between genetic variants
Support contact tracing investigations