Real-time tracking of RNA virus evolution and spread


Richard Neher
Biozentrum & SIB, University of Basel


slides at neherlab.org/201905_ECDC.html

GISRS and GISAID -- Influenza virus surveillance

  • comprehensive coverage of the world
  • timely sharing of data -- often within 2-3 weeks of sampling
  • hundreds of sequences per week (in peak months)
→ requires continuous analysis and easy dissemination
→ interpretable and intuitive visualization

nextflu.org

joint project with Trevor Bedford & his lab

Visualization features of nextstrain

  • Regular and time scaled phylogenies
  • Mutations are mapped to the tree
  • Filtering to time interval, region, country, authors, ...
  • Zoom into clades
  • Information on specific viruses
  • Color by amino acid or nucleotide
  • Frequency trajectories of clades and mutations
  • Color by antigenic advance, predictive scores, etc
Hadfield et al, 2018

Integrating antigenic and molecular evolution

  • each branch contributes $d_i$ to antigenic distance
  • sparse solution for $d_i$ through $l_1$ regularization
RN et al, PNAS, 2016

HI distances on the phylogenetic tree

Phylodynamic analysis with nextstrain

  • input: metadata (csv table) + sequences
  • snakemake pipeline
    • filtering
    • alignment
    • tree building (+time scaled trees)
    • ancestral state reconstruction and phylogeography
  • export to visualization
  • runs in minutes to 1h
Hadfield et al, 2018

Web visualization with nextstrain

  • fairly easy to set-up
  • can be run locally (localhost)
  • or be deployed on your own servers
  • work in progress:
    • flexible branding
    • drag and drop features
    • (better docs...)
Hadfield et al, 2018

Acknowledgments

  • Trevor Bedford
  • Colin Megill
  • Pavel Sagulenko
  • Sidney Bell
  • James Hadfield
  • Wei Ding
  • Emma Hodcroft
  • Sanda Dejanic