European Life Sciences Infrastructure for Biological Information www.elixir-europe.org

ELIXIR and the Grand Challenges

ELIXIR

Janet Thornton

A European Infrastructure for

Biological Information

ELIXIR

Genome

Embryo Cell

Fruitfly

Protein

Mouse Human

Development,

Ageing, Disease

The Grand Challenges

• Health • Changing demographics

• Healthy ageing – extending healthspan

• Infectious diseases

• Agricultural • Feeding a growing population

• Food security

• Managing in changing climates

• Environment • Maintaining Biodiversity

• Biofuels

We have been living through a revolution.

One genome 2003 to 2013

All living things are made from (DNA, RNA, Protein…)

There has been a huge impact on biological research

We are starting to have an impact on Medicine…

And agriculture, and the environment

European Life Sciences Infrastructure for Biological Information www.elixir-europe.org

ELIXIR and Health Challenges

ELIXIR

Janet Thornton

Current Human Variation Projects

• Many disease cohorts

• 100,ooo whole genomes in UK

• Finnish Project - to sequence 8000 Finns

• Faroe Islands – to sequence all population (50K)

• German and Spanish large scale cohorts

• International Cancer Genome Consortium - 20,000 high coverage genomes in 5 years for research

• Many others…….

Variants associated with coronary heart disease

Molecular Basis of Disease Consequences of mutations

p53 tumour suppressor

core domain - cancers of many types

Cu-Zn Superoxide

Dismutase - Autosomal dominant

Amyotrophic lateral sclerosis

Heart disease: finding people at risk

• By , almost 0.5% of our population is at high risk for developing heart disease.

• If they knew their risk by , they’d have a chance to beat it.

MRSA

• We can use DNA sequencing to clearly identify infectious bacteria

• Same technology can sequence the hospital environment

• Powerful information for containment response

• “Immune systems for hospitals”.

• Reference resources provided by ELIXIR

Tracking food-borne pathogens

• 2011 outbreak of E-coli O104:H4 infection

• responsible for more than 4000 cases and 50 deaths

• Origin initially linked to cucumbers

• Collaborative genome sequencing to identify pathogen and cause of virulence.

• Origin traced to bean sprouts

Discovery Development

Designing Novel Alzheimer’s Drugs

Clinical

Testing

Target

Discovery &

Validation

Drug

Validation

Drug

Discovery

ELIXIR will be involved at every stage – taking care of the data

European Life Sciences Infrastructure for Biological Information www.elixir-europe.org

ELIXIR and Agricultural Challenges

ELIXIR

Janet Thornton

Provision

of reference

genomes

Impact of genomics on Agriculture & Environment

Accelerated crop

improvement:

- quality

- yield

- disease resistance

- changing conditions

Understanding the

genetics

responsible for

agronomic traits

New strategies

for pest and

disease control

Ecosystem

genomics

Biodiversity

management and

conservation

1 2

4

Future fuels

Maximising the

efficiency of

biomass

processing

3

Developing Drought resistant varieties

• Drought resistance is a complex

trait, controlled by several genes.

• Identify genomic regions

associated with drought

tolerance in wheat – useful in

marker-assisted breeding.

• Re-introducing genes from wild

wheat relatives from the Middle

East into modern varieties.

Tomato variation

SUN, OVATE,

FAS and LC genes

make major

contributions to

differences in fruit

shape.

Sequencing the tomato genome

• Identification of the parts of the

genome responsible for desirable

features and characteristics

responsible for evolutionary success.

• This understanding will lower costs and

accelerate efforts to improve global

tomato production.

• Lead to varieties better equipped to

combat pests, droughts and diseases.

Breeding robust staple crops

Sustainable bioenergy: genomics and biofuels development

• Genomics provides a better

understanding of how to harness

various renewable energy sources,

• Sequencing of potential biofuels:

miscanthus, poplar and willow

• Genetic engineering of enzymes

for optimising the development of

sustainable biofuels.

European Life Sciences Infrastructure for Biological Information www.elixir-europe.org

ELIXIR and Data Challenges

ELIXIR

Janet Thornton

Future Scale of Genomic Data

1 Human Genome is 109 bases Human genome for all UK citizens - 65m x 109 = 6x1016

SNPs for all UK citizens - 65m x 106 = 6x1013 1 petabyte = 1015 EBI currently has ~30 petabytes of storage

3 petabytes

of raw data

every day

9

petabases

of DNA

every week

5 million

births per

year

Sequencing every child born in the EU?

Storing only

variants: much

more feasible

Data islands

?

Data Challenges Format, Ontologies, Security, Links to clinical records, Data Flow

Infrastructure will be needed to deliver the benefit to the patients and also to the academic research and commercial communities will include: • Infrastructure re samples – collection of samples; delivery from hospital to sequencing

centre; delivery of data from sequencing centre to NHS database

• Database to store the genomic data and deliver to users

• Tools to annotate the data

• Generic annotation – by comparison to public reference databases

• Disease specific clinically actionable annotation

• Tools to deliver the data to the clinicians and to integrate data with clinical data

• Tools to provide download of specified data to academics and commercial entities

BioMedBridges

Ten new biomedical sciences research

infrastructures: stronger through common links

Computational ‘data and

service’ bridges between the

BMS RIs

Interoperability between data

and services in the biological,

medical, translational and

clinical domains

Link basic biological research

data with clinical research and

associated data

35

BioMedBridges

will deliver:

Data bridges

Creating links between available data that were not linked before will hugely increase the potential for new discoveries

Interoperability bridges

standards, formats, ontologies... and how to make it linkable!

Social bridges

Connecting the biomedical research infrastructures

Image courtesy of MDOT's Photography

Unit.

European Life Sciences Infrastructure for Biological Information www.elixir-europe.org

ELIXIR and Innovation

ELIXIR

Janet Thornton

ELIXIR & Innovation

DNA as Storage Medium

Interpreting Genomes

Designing new Enzymes

Into the Clinic & Environment

New Drugs