Data integration, real-time pipelines and visualization strategies


Trevor Bedford (@trvrb)
4 Oct 2017
ARTIC Network Meeting
University of Edinburgh

This talk

Studies of Ebola phylogenetics published alongside outbreak

Carroll et al. 2015. Nature., Park et al. 2015. Cell., Arias et al. 2016. Virus Evol., Quick et al. 2016. Nature.

Difficult to extract a comprehensive picture from these studies

Comprehensive analysis published in Apr 2017 (on bioRxiv Sep 2016)

Dudas et al. 2017. Nature.

There have also been publications on the ongoing Zika epidemic

Metsky et al. 2017. Nature., Grubaugh et al. 2017. Nature., Faria et al. 2017. Nature.

There currently does not exist a comprehensive Zika phylogeny in the literature (or bioRxiv)

  • Trees in these papers used 174, 104 and 200 genomes, respectively
  • There are now 542 genomes in Genbank

Even if these genomes did not change the story told by these papers, they could improve credible intervals and connect dots not available to the original papers

Outline

  • What we're trying to do
  • Brief overview of approach
  • Design choices we've made

nextstrain

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


with Richard Neher, James Hadfield, Colin Megill,
Sidney Bell, Charlton Callender, Barney Potter,
and John Huddleston

Timeline

Key challenges

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

Nextstrain architecture

All code open source at github.com/nextstrain

Fauna

Rethink database of virus and titer data

  • Harmonizes data from different sources
  • Integrates different types of data (serology, sequences, case details)
  • Provides an interface for downstream analysis

Augur

Build scripts to align sequences, build trees and annotate

  • Flexible build scripts to incorporate different viruses and analyses
  • Constructs time-resolved phylogenies
  • Annotates with geographic transitions and mutation events

Example augur pipeline for 1600 Ebola genomes

  • Align with MAFFT (34 min)
  • Build ML tree with RAxML (54 min)
  • Temporally resolve tree and geographic ancestry with TreeTime (16 min)
  • Total pipeline (1 hr 46 min)

Auspice

Web visualization of resulting trees

  • Interactive data exploration and filtering
  • Framework through React / D3
  • Connects phylogeny, geography and genotypes

Analysis targets

  • Phylogeny
  • Mutations present
  • Geographic transitions
  • Root-to-tip plot

Example from Faria et al

Faria et al. 2017. Nature.

Example from Metsky et al

Metsky et al. 2017. Nature.

nextstrain.org

Viz strategies

Core of visualization is the ability to make comparisons

Color to link attributes across panels

Details on demand

Transitions to maintain object constancy

Filtering time, space and other attributes

Viz challenges

  • Recombination / reassortment
  • Combining fragments with full genomes
  • Combining metadata of varying resolution
  • Conveying uncertainty

Importance of curation by domain experts

Public dissemination vs on-site investigation

Acknowledgements


Nextstrain software development: Richard Neher, James Hadfield, Colin Megill, Sidney Bell, Charlton Callender, Barney Potter, John Huddleston

Advice / support: Andrew Rambaut, Nick Loman, Ian Goodfellow, Matt Cotten, Paul Kellam, Kristian Andersen, Nathan Grubaugh, Pardis Sabeti