Pipeline components for real-time virus analysis

Introduction

The nextstrain project is an attempt to make flexible informatic pipelines and visualization tools to track ongoing pathogen evolution as sequence data emerges. The nextstrain project derives from nextflu, which was specific to influenza evolution.

nextstrain is comprised of three components:

  • fauna: database and IO scripts for sequence and serological data
  • augur: informatic pipelines to conduct inferences from raw data
  • auspice: web app to visualize resulting inferences

Augur

Definition: One held to foretell events by omens.

Augur is the informatic processing pipeline to track evolution from sequence and serological data. It aims to

  • subsamples, cleans and align sequences
  • build a phylogenetic tree from this data
  • infer ancestral states
  • infer timing of phylogenetic branching events
  • infer mutation and clade frequency trajectories through time
  • export a JSON bundle for visualization

Format of JSON outputs

tree JSON

Augur outputs the tree as a JSON file modeled after the format used by d3. { strain: 'name of virus or internal node', clade: 1, //clade identifier, typically an integer xvalue: 0.052, //tree layout: divergence from root yvalue: 251, //tree layout: vertical position in tree tvalue: 6.25 //tree layout: years since root, num_date attribute can be used instead muts: [ ('A135G'), () ...], //nucleotide mutations mapped to branch aa_muts: { //amino acid mutations mapped to branch 'protein1':[ ('F155Y'), () ...]}, 'protein2':[] }, attr: { region: "africa", //top level geo country: "nigeria", city: "lagos", num_date: 2015.14, // numerical date date: 2015-02-13 //YYYY-MM-DD date string div: 0.052, //divergence from root // any other attributes that auspice needs to know } children:[ { strain: ... }, { ... }, ] }

sequence JSON

The input sequences are stored in a compressed JSON format as follows: { root: { //the sequence inferred for the root node nuc: "ACGAGTGATG...", protein1: "KCYTWD...", protein2: "ASRTRTY...", }, 1: { // sequences for each node in the tree (incl the root) // these can either be full sequences or differences relative to root nuc: { 135:"G", 225:"A"}, protein1: {155: "Y"}, ... }, 2: { ... }, ... }

frequency JSON

{
    pivots: [2013, 2013.25, 2013.5 ...],     //interpolation pivots for frequency trajectories
    // identifier format: region_category:position
    "global_protein1:135Y"  : [0.0, 0.1, ...],    //frequencies at the pivots points
    "global_nuc:135G"       : [0.0, 0.1, ...],    //nucleotide mutation frequencies
    "global_clade:2"        : [0.0, 0.1, ...],   //clade frequencies
}

License and copyright

Copyright 2014-2016 Trevor Bedford and Richard Neher.

Source code to nextstrain is made available under the terms of the GNU Affero General Public License (AGPL). nextstrain is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU Affero General Public License for more details.