Global surveillance of infectious diseases Open science, open data, - - PowerPoint PPT Presentation

Global surveillance of infectious diseases Open science, open data, open for all

Frank M. Aarestrup www.compare-europe.eu www.genomicepidemiology.org

The charge of the light brigade

Strategy to win a war

Putting up the right defense

Knowing: Where What When How Communicate & Prioritise

IMPORTANCE OF INFECTIOUS DISEASES

• Direct cause of 22% of all global deaths (15 million)
• Huge burden on expected life length and disability (DALYs)
• Devastating effects on economy:
• Absence from work
• Trade
• Travel
• Health system
• Expected to increase; e.g. AMR alone causing 10 million deaths in

2050 (cancer 8.2 million in mainly older people)

Current infectious disease situation

• Dynamics of common infectious diseases are changing

– Demographic change, population density, anti vaccine, AMR, etc.

• New diseases / variants emerge frequently

– Population growth, travel, trade, climate change

• Effects are difficult to predict due to complexity

– Rapid flexible response

• Public health, diagnostic, vaccine development and clinical

response depend on global capacity for disease surveillance

– Rapid sharing, comparison and analysis of data from multiple sources and using multiple methodologies

2 main aspects

§ Most EID come from animals,

• pportunity for contact increases

§ Once introduced in people, many

• pportunities for transmission

Wolfe et al., 2007; http://rambaut.github.io/EBOV_Visualization/Makona_1561_D3/; Gytis et al., 2017

§ Complexity increased by food trade

Ambition: Reduce impact of EID by improving prediction, prevention, detection, control and treatment

Response to ID outbreaks usually fragmented and late

9

Infected patients

Public Health response Preclinical research response

time

clinical research response Adapted from:

Courtesy Frank Deege

Response to ID outbreaks with improved detection and sharing of data

10

Infected patients

Public Health response Preclinical research response

time

clinical research response

Courtesy Frank Deege

NGS advantages

• Laboratory diagnostics increasingly rely on (pathogen) genomic

information

• RNA / DNA are common across pathogens, therefore, methods to

analyse pathogen genomes are potentially universal

• Next generation sequencing capacity is developing fast, and costs are

becoming competitive

• Data are easy to share electronically and are in a standardized format

Ø Capturing NGS developments may provide a universal language that can be harnessed for early detection of outbreaks across disciplines and domains Ø If the technology keeps developing, less equipped labs may leapfrog

Preparing for Global Surveillance - Center for Genomic Epidemiology (CGE)

• Provide a proof of concept of combining bioinformatics with global

epidemiology in real-time (2010-2016)

• Provide foundation for web based solutions (plug and play tool)

– Rapid sequence assembly and annotation

• What is it
• How dangerous is it
• Have we seen it before
• Can it be treated
• www.genomicepidemiology.org

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643476.

http://cge.cbs.dtu.dk/services/all.php

CGE tool box

CGE Batch upload – simple upload and ”all in one go”

1 4 12 June 2017

Uploaded data and analysis easy to search and download

User Statistics

Until now: >1,000,000 submissions from 15,000 IP- adresses in +100 countries

Moving tools to the data – integration into ENA repository

Why a central public repository?

Besides the language and altruistic issues

• The data comparison problem
• Allowing easy transfer between levels of access

including public

• Allow access to bioinformatics for the frontline
• Allowing for constantly improving the analytic

pipelines

Data comparison problem

Global repositories > 0.1 - 10 Pb data Client ~1-100 Gb data Internet ~1-10Gb/hour Bring the tools to the data

mcr-1

• Mcr-1 gene added to ResFinder database on Nov. 24
• Nov. 25 – screening of online available human and food

isolates initiated using an iphone on a plane to Paris – 5 hits

• Nov. 25-26 the authorities notified and the screening

extended to +3,000 available genomes

• Nov. 29 meeting with the authorities – please wait
• Dec. 2 press release and submission of manuscript
• Dec. 9 publication

Establishing and improving real-time surveillance

• Rapid sharing

– Online bioinformatic tools

• >1,000 jobs per day

– Facilities for rapid sharing

• Natural reservoirs

– Major issues with individual samples

20

The Rio Convention The Nagoya Protocol National ethical committees

Global sewage surveillance - 2016

12 June 2017

India Brazil

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643476.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643476.

R² = 0,30873

10 12 14 16 18 20 22 24 26 28 30

50 100 150 200 250 300 350 400 450

AMR

Copenhagen according to sewage

Samples collected since Nov. 2015 Sequenced routinely since June 2016 Released publicly real-time Very preliminary data Drug use the previous year

Global sewage 2017

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643476.

Global surveillance of:

• Healthy humans
• Healthy animals
• Diseased humans & animals

Explanatory varaibles:

• Trade (food)
• Travel (flight)
• Demographic (World bank)

1000 cities 1000 slaugtherhouses 50,000 laboratories

Building a global genomic epidemiological infrastructure – making data assessable Data:

• World Bank

(demographic/economic)

• WHO (health)
• FAO (food production and

trade)

• Flight connections
• Antimicrobial use

Own data Online epidemiological tools (epidemiology for dummies) Search and download Own analysis Raw NGS data Sharing site

• Own data
• Shared data
• Public data

Online bioinformatic tools

(Bioinformartics for dummies)

• Assembly
• Mapping
• Phylogeny

Research is not enough

• E-learning

– Massive Open Online Courses

• Ring-trials
• Advisory service
• No free ride

– If you will not share – pay

46 laboratories in 22 countries have provided data for at least one of the PT components

Challenges

• Scientific

– Make sense (or even analyse) +50 million genes among exabytes data explained by +2,000 variables and global connectivities

• False discovery rate – min. 5 billion using clasical statistics
• Sustainability/analytic pipeline

– 500 million € to establish, 50 million €/y to run

• Sharing of data
• Scientific credit
• Political and other consequences

– When we report diseases where they should not exist!

How to get involved

• Build a database and work with us
• Come with some interesting questions and engage us
• Make a pipeline and challenge us
• Support us financially

– 500 million € to establish, 50 million €/y to run – I will be standing outside accepting collections

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643476.

Guiding principles:

• Cross sector, cross domain, open source (not commercial)
• Interaction with the rest of the world (all inclusive)
• Data for action (actionable outputs)
• Central repository (tools to the data) (ENA, DDJ,NCBI)

Our vision: one system serves all

There can be no real-time disease surveillance without real-time data sharing

Kingdom Phylum Class Family Genus Species IKEA-BigMac Lyngby-Whopper Eukaryota Chordata Mammalia Bovidae Bos Bos mutus 47,728767 55,138006 Eukaryota Chordata Mammalia Bovidae Bubalus Bubalus bubalis 16,571103 16,052984 Eukaryota Chordata Mammalia Bovidae Capra Capra hircus 0,779368 0,858108 Eukaryota Chordata Mammalia Bovidae Ovis Ovis aries 0,362244 0,592654 Eukaryota Chordata Mammalia Vespertilionid ae Myotis Myotis davidii 0,286175 0,062029 Eukaryota Chordata Mammalia Muridae Rattus Rattus norvegicus 0,165231 0,151688 Eukaryota Chordata Mammalia Macropodidae Macropus Macropus eugenii 0,153902 0,189751 Eukaryota Chordata Mammalia Bovidae Pantholops Pantholops hodgsonii 0,129919 0,102347 Eukaryota Chordata Mammalia Bovidae Bos Bos taurus 0,088133 0,203566 Eukaryota Chordata Mammalia Balaenopterid ae Balaenoptera Balaenoptera acutorostrata 0,077098 0,045253 Eukaryota Chordata Mammalia Ursidae Ailuropoda Ailuropoda melanoleuca 0,012359 0,008599

Complete sequencing of food products