Meeting the global challenge of food securityBioinformatics in the animal health and welfare sector

Mick WatsonDirector of ARK-Genomics

The Roslin Institute

Structure• The Roslin Institute• Challenges in global food security

– John Beddington’s “Perfect Storm”

• Current technologies and research• Bioinformatics• The future

The Roslin Institute

Bioscience underpinning healthLIVESTOCK GENETICS

ANIMAL HEALTH

BIOTECH

HUMAN HEALTH

Food security

The Roslin Institute: AimsEnhance animal health and welfare through knowledge animal geneticsEnhance sustainability and productivity of livestock systemsEnhance food safety by understanding host-pathogen interactionsEnhance human health through an understanding of diseaseIdentify new and emerging zoonosesEnhance quality of life for farmed animals

C. McKenzie

Highlights

Wilmut at al (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385(6619):810-3Zhao et al (2010) Somatic sex identity is cell autonomous in the chicken. Nature 464(7286):237-242Lyall et al (2011) Suppression of avian influenza transmission in genetically modified chickens. Science 331(6014):223-6

CHALLENGES IN FOOD SECURITY

Challenges in food security• The World’s food system doesn’t work:

– 1.5bn overweight, 500m obese1

– 925m experience hunger, +1bn “hidden hunger”2

• Moving forward, there are a number of key pressures:

1. WHO [http://www.who.int/mediacentre/factsheets/fs311/en/]2. Foresight report “The Future of Food and Farming: Challenges and choices for global sustainability”

The Issues• Population: rising to 9bn by 2050 • Consumption of meat set to double in the

same time frame• Net exporters may become net importers• Food superpowers: Brazil, China, India, Russia• Agriculture contributes up to 30% of all

greenhouse gases• Competition for resources: land use, energy,

water• Ethical issues: GM, organic, animal health and

welfare

2010 2030 20506,000,000,000

7,000,000,000

8,000,000,000

9,000,000,000

Should we be worried?

• Yes and no! Humans have been improving food for many centuries• Note: no information for beef cattle and sheep

A genomics / genetics experiment• Choose / measure phenotype, determine heritable• Discover variation• Measure that variation in many thousands of individuals

– Case / control

• Select markers, design smaller panel• Use smaller panel in selection, breeding or diagnostic

• Select markers and hunt for functionWellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 447(7145):661-78

Human vs Vet Genomics• The human genome attracts a lot of attention– Encode, 1000 genomes

• Farmed animal genomes need considerable attention– Functional annotation

• Imbalance of funding– MRC, Wellcome, DoH, Cancer charities, Big Pharma– BBSRC, Vet Pharma, Breeders

• Needs are similar, except– Vet health: more animals, more diseases– We can GM and breed– We’re trying to do the same less funding

ARK-GENOMICS

ARK-Genomics: TechnologiesDNA Sequencing

Illumina Sequencing• Up to 150bp paired• Novel genomes• Resequencing• RNA-Seq• ChIP-Seq• Epigenetics

Illumina HiSeq 2000Sanger 3730

GenotypingIllumina - from HD tocustom chips• iScan, Inifinium• BeadXpress, Goldengate• BeadChip

Affymetrix• GeneTitan, Axiom• Process 96 arrays / run

MicroarraysGene Expression• Affymetrix• Agilent• Illumina• Whole genome• Exon-level• microRNA

CGH, ChIP-Chip, MeIP• Nimblegen

Current research• Genome (re)sequencing

– Sheep genome with BGI– 21 chicken genomes

• With IAH: disease resistance• With breeders: design SNP chip

– Bacterial genomics • Functional genomics

– Interaction between host and viral TFs and microRNAs during avian viral oncogenesis

• Metagenomics– Gut microbiome: : the “forgotten organ” – Ruminants are exceptional at gaining protein and energy from plants

Are we prepared now?• (Re)sequencing

– BWA, Novoalign

• De novo assembly– Velvet, SOAPdenovo

• Functional Genomics– Bioconductor, CORNA

• Metagenomics– MetaVelvet, MetaGene

• Technical– MISO (LIMS), Commercial– Galaxy, Taverna, Pipeline Pilot

BIOINFORMATICS

What is Bioinformatics?• Within ARK-Genomics, it is a research tool

– Turn data into knowledge and information– We (re)use open-source software– We only develop new software where is absolutely, positively does not

exist elsewhere

• Are we (ARK-Genomics) prepared?– Software – yes– People…?– We have good people– Do we have enough?– Are they easy to find?

Data analysis

LIMS

Storage

What is Bioinformatics?• Dayhoff, M. O. and R. S. Ledley (1962). Comprotein: A Computer Program to Aid Primary

Protein Structure Determination. In Proceedings of the Fall Joint Computer Conference, 1962, 262-274.

• J. M. Bennett and J. C. Kendrew (1952). The computation of Fourier synthesis with a digital electronic calculating machine. Acta Cryst. 5, 109-116

• Fisher, R. A. (1950) Gene frequencies in a cline determined by selection and diffusion. Biometrics 6: 353–361.

• Types of bioinformatician?1) The software developer 2) The statistician 3) The data miner/analyst 4) The database developer

• Is a bioinformatician “all of the above” plus knowledge of biology?

• What should we teach?

How do we “provide” bioinformatics?• In-house– Vs

• Out-source– Vs

• Community

• A combination of the above?

Bioinformatics grand challenge• Enabling non-expert users

THE FUTURE

Future Technologies• Third-generation sequencing (TGS)• Single molecule sequencing

• Challenges– Each observation relates to zero, one or more realities– Technology-aware software

The Promise The current reality

Billions of reads ~80,000 reads

10,000 – 50,000 read length 30bp, up to 1000bp

High accuracy > 5% error rate

Branton et al (2008) Nat. Biotech. 26(10):1146Schadt et al (2010) Hum. Mol. Gen. 19(R2):R227

Future technologies• There are no “game changers” yet

– Helicos– Pacific Biosciences

• There’s a complex IP landscape

• What will we do when we no longer have to assemble things?– Functional, statistical– Closer to function

Future Bioinformatics• Will technology providers give us more than just data?

• “In our nanopore technology development, we focus on the need to improve overall workflows that deliver experimental results to the end user, not just the molecular analysis part of an experiment.“– Clive Brown, Chief Technology Officer, Oxford Nanopore.

Personal / individual genomics• 1000 genomes data – petabyte scale• TGS will enable entire scans of genomes,

transcriptomes and epigenomes in minutes• Huge data potential – exabyte scale

• "Provisioning Bioinformatics for the Next Decade – are we prepared?“

• “NGS” arrived 2007/8• No-one predicted NGS in 2001 (ten years ago)• Therefore we cannot predict what we will come up against• TGS represents specific challenges

– Large Data Storage– Technology-aware software– Enables new assays and new science

• We would have said the same about NGS….• These are not new problems, but will require new solutions• There is a lag between technology and software….

• Providing bioinformaticians for the next decade….

• The term bioinformatician means many things• Many require a wide range of skills• Others require a depth of specific skills• The best thing we can teach is the ability to learn and

adapt• There is a definite skills shortage• There always has been

Summary• There are significant challenges in feeding the growing

population• Genetics and genomics can help• There is a funding gap• Current bioinformatics is well provisioned

– Though there is a shortage

• New technologies will re-open old problems– We will require new solutions

• We need continued investment in bioinformatics• We need more and better qualified staff