The use of WGS data for surveillance

systems: the Canadian experience Gary Van Domselaar Chief, Bioinformatics

National Microbiology Lab

Public Health Agency of Canada

11 May 2016

The NML’s Current Enteric Disease Surveillance Program

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NATIONAL MICROBIOLOGY LABORATORY

PROVINCIAL PUBLIC HEALTH LABORATORIES

CLINICAL ISOLATES

SENTINEL SURVEILLANCE (FoodNet Canada)

CLINICAL, FOOD, ENVIRONMENTAL

CANADIAN FOOD INSPECTION AGENCY

(Regulatory)

FOOD ISOLATES

LISTERIA - E. COLI O157:H7 - SALMONELLA - SHIGELLA

PFGE/MLVA

PUBLIC HEALTH ACTION

Early Work in WGS for Outbreak Investigation: Listeria 2008

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Early Work in WGS for Outbreak Investigation: Haiti Cholera Outbreak 2010 -

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GRDI Shared Priority Project on Food and Water Safety 2012

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PulseNet Genomic Epidemiology Roadmap

PulseNet Canada

Genomic

Epidemiology

Roadmap

Aleisha Reimer with contributions from Drs Celine

Nadon, Morag Graham, and PulseNet Canada

members

October 16, 2013

Based on existing PulseNet model

De-centralized sequencing and

analysis

Parallel, centralized storage & analysis of

national data sets

Continued NML support in reference

testing, training, certification &

proficiency

Continued method development,

refinement, and KT

Implementation Plan

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Implementation

Retrospective

Study

Prospective Study

Surveillance Outbreak

Response

Baseline Data

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Pilot Projects: Retrospective and Prospective Studies

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Overview of Retro1000 Project

DELIVERABLES 1. Expanded and accessible national database of draft genomes 2. Standardized/harmonized procedures for sample prep, sequencing, bioinformatics analysis, and quality

control – including interlaboratory validation 3. Interpretation criteria and/or elements for proper use of WGS data for public health 4. Quarterly and final reports

Select isolates for sequencing (n=1000 each)

NGS (Illumina MiSeq)

Analysis (SNVPhyl and

wgMLST)

Conclusions and Reporting

APPROACH

Inter-laboratory comparisons

Procedures, criteria,

recommendations

Organisms selected by

PNC Steering

Committee

# isolates already

Sequenced

Listeria monocytogenes 400

E. coli O157 530

S. Enteritidis 21

S. Typhimurium 0

S. Heidelberg 66

S. Thompson 429

Overview of Retro1000 Project

Real-time Investigations Supported by WGS, PulseNet Canada 2014

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Organism Case or Outbreak Details

(putative/confirmed vehicle)

L. monocytogenes Collaboration with USA (lettuce product)

L. monocytogenes Collaboration with USA (RTE meat

product)

Salmonella

Thompson

National laboratory investigation to

support outbreak response in a single

province – see sidebar (potential

chicken products)

E. coli O157:H7 Large outbreak in a single province

(pork products)

L. monocytogenes Ongoing cluster of common PFGE

pattern

L. monocytogenes Collaboration with USA (caramel

apples)

S. Enteritidis Collaboration with USA (bean sprouts)

National

Public Health Agency

Provincial

Public Health AgencyAcademic/Public

Partnership among provincial public health agencies, national public health agencies and academic institutes to bridge the gaps between advancements in genomic epidemiology

and real-life and real-time use cases in public health agencies - Project Team has direct access to state of the art researches in academia

- Project Team is directly embedded in user organization

IRIDA Design

• Carefully designed and engineered software platform is just the starting point… User

Interface

Secu

rity

File system

Metadata Storage

Application logic

REST API Workflow Execution Manager

Continuous Integration Documentation

Canada’s Byzantine Public Health System

Source: M. Taylor, BCCDC

Provincial public

health dept.

National laboratory

Local public

health dept.

Provincial

laboratory

Cases

Physicians Frontline lab

Information

Bio

info

rmatics an

d A

nalytical C

apacities

Local Storage

Remote APIs

IRIDA’s Federated Design

List Samples

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Application Ontology Controls Metadata

Build On, Work With: OBI TypON NGSOnto NIAID-GSC-BRC core metadata MIxS Ontology NCBI Biosample etc TRANS – Pathogen Transmission EPO Exposure Ontology Infectious Disease Ontology CARD, ARO for AMR USDA Nutrient DB EFSA Comp. Food Consump. DB

Example gaps to be filled: Expand food ontology; expand CARD AMR data with others.

Analytical Tool

Quality Control Module

Quality Metrics

Quality Control

IRIDA’S QA/QC Model

IRIDA Workflows: Portable and Transparent Pipelines

• Use Galaxy as workflow engine – large community support

• Retools to address usability, security, and other limitations

• Version Controlled Pipeline Templates

• Input files, parameters, and workflow are sent to IRIDA-specific Galaxy for execution

• Results and provenance information are copied from Galaxy

1. Input files sent to

Galaxy

3. Results downloaded from Galaxy

IRIDA UI/DB

Galaxy

Assembly Tools

Variant Calling Tools

…

REST API

Shared File System

Worker Worker

2. Tools executed on Galaxy workers

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IRIDA Pipelines: SNVPhyl

Genomic Surveillance of

Antimircrobial Resistance 20

IRIDA Pipelines: Genomic Surveillance of AMR

SISTR: THE SALMONELLA IN SILICO TYPING RESOURCE │ https://lfz.corefacility.ca/sistr-app/

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In silico analysis of WGS data assembly statistics

serovar prediction

in silico typing (MLST, cgMLST)

AMR prediction

Comparative genomic analyses cgMLST

accessory gene content

core SNPs

Epidemiologic analysis geospatial distribution

temporal distribution

source association

External Access via REST API

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http://pathogenomics.sfu.ca/islandviewer

IslandViewer

Dhillon and Laird et al. 2015, Nucleic Acids Research

http://kiwi.cs.dal.ca/GenGIS

Parks et al. 2013, PLoS One

When will it be available?

• Jun 1 2015: IRIDA 1.0 beta internal release – Release to collaborators for installation and full test

• Jul 1 2015: IRIDA 1.0 beta1 – Announce Beta release, download, documentation

available on website – www.irida.ca

• Aug 1 2015: IRIDA 1.0 beta2

– Cloud installer, with documentation – Additional pipelines as available – Visualization as available

Outbreak investigation Routine surveillance

Canada’s long-

term vision

Acknowledgements Project Leaders

Fiona Brinkman – SFU Will Hsiao – PHMRL Gary Van Domselaar – NML University of Lisbon Joᾶo Carriҫo National Microbiology Laboratory (NML) Franklin Bristow Aaron Petkau Thomas Matthews Josh Adam Adam Olsen Tara Lynch Shaun Tyler Philip Mabon Philip Au Celine Nadon Matthew Stuart-Edwards Morag Graham Chrystal Berry Lorelee Tschetter Laboratory for Foodborne Zoonoses (LFZ) Eduardo Toboada Peter Kruczkiewicz Chad Laing Vic Gannon Matthew Whiteside Ross Duncan Steven Mutschall

Simon Fraser University (SFU) Melanie Courtot Emma Griffiths Geoff Winsor Julie Shay Matthew Laird Bhav Dhillon Raymond Lo BC Public Health Microbiology & Reference Laboratory (PHMRL) and BC Centre for Disease Control (BCCDC) Judy Isaac-Renton Patrick Tang Natalie Prystajecky Jennifer Gardy Damion Dooley Linda Hoang Kim MacDonald Yin Chang Eleni Galanis Marsha Taylor Cletus D’Souza Ana Paccagnella University of Maryland Lynn Schriml Canadian Food Inspection Agency (CFIA) Burton Blais Catherine Carrillo Dominic Lambert Dalhousie University Rob Beiko Alex Keddy

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McMaster University Andrew McArthur Daim Sardar European Nucleotide Archive Guy Cochrane Petra ten Hoopen Clara Amid European Food Safety Agency Leibana Criado Ernesto Vernazza Francesco Rizzi Valentina