Phylodynamics to assist in Ebola outbreak response


 

Trevor Bedford (@trvrb) and Allison Black (@alliblk)
4 Dec 2019
Epidemics7
Charleston, SC
 
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Pathogen genomes can reveal transmission dynamics

Key challenges to making genomic epidemiology actionable

  • Timely analysis and sharing of results critical
  • Dissemination must be scalable
  • Integrate many data sources
  • Results must be easily interpretable and queryable

Nextstrain

Real-time tracking of pathogen evolution

with Richard Neher, James Hadfield, Emma Hodcroft, Thomas Sibley, Colin Megill, John Huddleston, Barney Potter, Sidney Bell, Louise Moncla, Charlton Callender, Misja Ilcisin, Kairsten Fay, Jover Lee

Nextstrain is two things

  • a bioinformatics toolkit and visualization app, which can be used for a broad range of datasets
  • a collection of real-time pathogen analyses kept up-to-date on the website nextstrain.org

Ongoing DRC outbreak

Genomic epidemiology applied to North Kivu Ebola outbreak

with Placide Mbala-Kingebeni, Eddy Kinganda Lusamaki, Catherine Pratt, Mike Wiley, James Hadfield, Allison Black, Jean-Jacques Muyembe Tamfum, Steve Ahuka-Mundeke, Daniel Mukadi, Gustavo Palacios, Amadou Sall, Ousmane Faye, Eric Delaporte, Martine Peeters and many others

Nextstrain is being used to track North Kivu outbreak

Allison Black (PhD student) and James Hadfield (postdoc) working with scientists at the INRB. Goal is to provide training in bioinformatics, Nextstrain and genomic epidemiology.

View of current genomic data

432 genomes most recent from late Oct

Often (but not always) need specific actionable pieces of information rather than large-scale understanding. For Ebola outbreak response, I believe this needs to revolve around contact tracing.

Superspreader event in June

To increase public health impact, we need good ways to communicate genomic findings to field epidemiologists

We think interpretation can be improved by providing information tied to specific views of the tree

Nextstrain now provides this type of view through support of "Nextstrain Narratives"

Narratives are written as Markdown files that link visualization with descriptive text

What are we looking for in the phylogenies?

Spatial patterns, sources, and sinks

How are cases connected?

     
Mutations Time
4 mutations 108 days
~0.59 mutations per serial interval ~13 days per serial interval
4/0.59 = ~7 serial intervals 108/13 = ~8 serial intervals

Example: Evidence for multiple concurrently circulating transmission chains in Kalunguta

Extraordinarily challenging outbreak, but some good things going on here

  • Samples sequenced entirely in country by local scientists
  • Bioinformatics for genome assembly and for phylodynamics run entirely in country
  • Nextstrain narratives to aid epidemiological interpretation
  • Best turnaround time so far is 7 days from sample collection to genomic situation report

Acknowledgements

Bedford Lab: Alli Black, John Huddleston, James Hadfield, Katie Kistler, Louise Moncla, Maya Lewinsohn, Thomas Sibley, Jover Lee, Kairsten Fay, Misja Ilcisin, Nicola Müller

Ebola in DRC: Allison Black, James Hadfield, Eddy Kinganda Lusamaki, Placide Mbala-Kingebeni, Catherine Pratt, Mike Wiley, Jean-Jacques Muyembe Tamfum, Steve Ahuka-Mundeke, Daniel Mukadi, Gustavo Palacios, Amadou Sall, Ousmane Faye, Eric Delaporte, Martine Peeters, David Blazes, Cécile Viboud

Nextstrain: Richard Neher, James Hadfield, Emma Hodcroft, Tom Sibley, John Huddleston, Sidney Bell, Barney Potter, Colin Megill, Charlton Callender