The use of WGS data for surveillance systems: the Canadian experience.

1. 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

2. The NML’s Current Enteric Disease Surveillance Program
2
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

3. Early Work in WGS for Outbreak Investigation: Listeria 2008
3

4. Early Work in WGS for Outbreak Investigation: Haiti Cholera Outbreak 2010 -
4

5. GRDI Shared Priority Project on Food and Water Safety 2012
5

6. 6
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

7. Implementation Plan
7

8. Implementation
Retrospective
Study
Prospective Study
Surveillance Outbreak
Response
Baseline Data
8
Pilot Projects: Retrospective and Prospective Studies

9. 9
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

10. 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

11. Real-time Investigations Supported by WGS, PulseNet Canada 2014
11
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)

12. National
Public Health Agency
Provincial
Public Health Agency
Academic/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

13. IRIDA Design
• Carefully designed and engineered software platform is
just the starting point… User
Interface
Security
File system
Metadata
Storage
Application
logic
REST API
Workflow Execution Manager
Continuous Integration Documentation

14. 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
BioinformaticsandAnalyticalCapacities

15. Local Storage
Remote APIs
IRIDA’s Federated Design
List Samples
15

16. 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.

17. Analytical
Tool
Quality Control Module
Quality
Metrics
Quality
Control
IRIDA’S QA/QC Model

18. 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

19. 19
IRIDA Pipelines: SNVPhyl

20. Genomic Surveillance of
Antimircrobial Resistance
20
IRIDA Pipelines: Genomic Surveillance of AMR

21. SISTR: THE SALMONELLA IN SILICO TYPING RESOURCE │ https://lfz.corefacility.ca/sistr-app/
21
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

22. External Access via REST API
24
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

23. 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

24. Outbreak investigationRoutine surveillance
Canada’s long-
term vision

25. 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
27
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