domselaar gmi8 beijing canadian wgs surveillance experience
TRANSCRIPT
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