will spooner - big data in mental health - 23rd july 2014

©Eagle Genomics Ltd

Big Data in Mental Health

23 July 2014

From 100,000 genomes to genomic medicine. OpportuniEes and challenges from an informaEcs perspecEve.

William Spooner, CSO, Eagle Genomics Ltd



"we should remain unabashed about the ul2mate impact of genomic medicine, which will be to transform the health of our children and our children’s children” – Eric Lander

Image: iStockphoto all rights reserved

Lander ES (2011). "IniEal impact of the sequencing of the human genome". Nature 479 (7333): 187–197.


Eagle; an Open Source Business

l  Consultancy/advice l  Training l  Support l  Installation/Integration l  Customization l  Out sourced management

Business Open Community (e.g. Academia) Service Company

Service CollaboraEon


About Eagle Genomics

Babraham-‐based consultancy InformaEcs: life science R&D Customers: US, Europe, Asia Collaborate: EBI, JIC, U.Man. Founded: 2008 Employees: 20

Solexa/Illumina

Horizon

Medimmune

AstraZeneca

Adenbrookes

Sanger/EBI

University

Babraham


The DNA Path

1 mile 10,000 leders 1 gene; BRCA2

BReast CAncer 2 Tumor suppressor

© Keith Edkins (CC BY-‐SA 2.0)


The Human Genome 3,000,000,000 leders 20,000 genes x10 round the world

© webdesignhot.com (CC SA 3.0)


Molecular Psychiatry advance online publica2on 30 August 2011; doi:10.1038/mp.2011.101

ScienEfic impact of genomics

Image: Sartr hdp://sartr.deviantart.com/gallery/?offset=96#/d1u0z75 CC BY-‐NC-‐ND 3.0

Phen

otype Associa8

on

©Eagle Genomics Ltd 14th October 2013 London Innovators 8

NRCAM


Mental health diseases with shared geneEc basis

•  100’s GWAS published for psychiatric disorders; –  Licit and illicit drug use, –  Schizophrenia, –  Bipolar disorder, –  Depression, –  Anorexia, –  OCD, PTDS, –  Tourede's, –  AuEsm, ADHD, …


Missing Heritability:!Linked allele!

v. Rare alleles !v. Polygenic Inheritance !

v. Epistasis!!


Need.!

More.!

Genomes!!!


About the 100K Genome Project

•  Announced by David Cameron in 2012, £100M funding •  Run by GeL, a private company 100% owned by DoH •  Sequence up to 100,000 paEents over next 5 years •  Focus on cancer and rare inherited diseases •  “UK will be the first ever country to introduce this technology in its mainstream health system”


100,000 Genomes by 2017


GeL Data Flows


Types of annotaEons anEcipated

•  Filtered ranked lists of variants with esEmates of pathogenicity

•  Expected impact at level of genes, pathways •  Tools organising literature around affected genes, pathways

•  Clear, simple clinical reports


10 GENOMES

July 23, 2014 Type footer in here 16

10 Human Genomes 2 TB sequence data 5 GB annotaEons


1,000 GENOMES

23/07/2014 17



100,000 GENOMES

23/07/2014 18



PaEents (consent) Sample

Tracking Biobank

Sequencing Centres

AnnotaEon Service Data

Control Service

Data Service

Clinical Data

Clinician

GeL Data Flows


PaEents (consent) Sample

Tracking Biobank

Sequencing Centres

AnnotaEon Service Data

Control Service

Data Service

Clinical Data

Clinician

Metadata Catalog


Eagle’s AnnotaEon Service Proposal


Annotate datafiles

Register datafiles

Data flow management with Eaglecore

Eaglecore Plaxorm

Eaglecore: plaxorm for the management of GeL metadata •  Secure •  CollaboraEve •  Scalable GeL-‐specific modules for: •  RepresenEng clinical NGS

experiments •  Automated workflows for

QC/annotaEon

GeL Ap

pliance

Share annotaEons

Register annotaEons

Progression


Automated annotaEon workflow

End

Generated data

AcEvity

Input data

Start

KEY

Output from one acEvity as input for a subsequent acEvity

Output report

Clinical ReporEng

Call variants

Alignment QC

Annotate variants

Gene annotaEon (Ensembl)

Alignment

Variation

SNV CNV SV

Alignment filter

Merge variants

Alignments BAM

Filtered Alignments BAM

Filtered Alignments BAM

Alignment Report HTML

Short variants VCF

Copy number variants VCF

Structural variants VCF

Short variants VCF

Copy number variants VCF

Structural variants VCF

Variants VCF Variants

Annotated variants TSV

Variant Report PDF

Annotated variants TSV

VCF

Annotation Disease annotaEon (DDD)

Custom annotaEon (100K Genomes)

Custom annotaEon (100K Genomes)


Web UI sFTP

Workflow Server Blackboard

Storage Instances only launched on workflow demand/load

elastic

Job fetching and status updating

Data input/output storage

Main data input/output Exchange for user access

Infrastructure AWS, OpenStack, …

Mas

ter i

nsta

nce

Scalable workflows with eHive


Variant Knowledge Base

Variant AnnotaEon with VEP

July 23, 2014

Ensembl Genes

Deciphering Developmental

Disorders

Thomson Reuters GVDB

100K Genomes

Sample VCF Ensembl VEP

Annotated Variants

VEP Plugin

VEP Plugin

VEP Plugin


ComparaEve Genomics

Regulatory Genomics

VariaEon

Assembly/Genes

Variant Storage with Ensembl

Data Integration

Data Reporting

Data Analysis

Data Integration

Data Querying

Data QC API

hdpd

DAS

Track Hub

VEP


Eaglecore Features

•  Metadata catalogue –  OrganisaEon of experimental

informaEon –  Links everything together in one place

•  Collabora8ve –  InformaEon easily and securely shared

•  Secure –  Enterprise soluEon –  Deployed on site or in the cloud

•  Scalable –  Designed to cope with the next

generaEon of assay technologies (e.g. NGS)

–  Designed to tackle data science

problems in life sciences R&D

•  Extensive search capabili8es –  Ontology support to standardise

entries for studies, phenotypes & technologies

•  API interface –  Allows connecEon to external

programs for further analysis

•  User friendly –  Easy-‐to-‐use interface for quick data

capture of new experiments & legacy data import

•  Open standards –  Uses established open standards (ISA,

OWL) & ontologies (e.g. EFO) to organise data


SegmentaEon of Commercial Users


Nurture Build trust, shared language

Collaborate Enterprise Academia Government FoundaEons Open

InnovaEon

Explore Work together to find a common

purpose

Exploit Turn ideas into

tangible benefits

29/ ElasEcAP, Pistoia Alliance Conference, Boston MA, 24th April 2012


GeL 100K Genomes

• Marker access, provider focus •  Personalised; companion diagnosEcs

Biomarkers in Clinical Trials

•  Link between target and disease •  Availability of predicEve biomarkers

•  StraEficaEon of paEent populaEon •  Cohort selecEon

Right target

Right paEent

•  PharmacokineEc/dynamic predicEon •  Pharmacogenomic biomarkers Right safety

Right market


Genomic Association [biomarker]

Towards Genomic Medicine

Personalised Medicine

Right drug

Right pa8ent

Right 8me

Pharmacogenomics

Genotypic

Transcriptomic

Epigene8c

©


GeL 100K Genomes, stats for mental health

•  GeL does not focus on mental health –  25,000 paired tumor/normal for cancer –  15,000 trios for rare disease

•  But, 1 in 4 with mental illness? –  Expect over 15,000 cases – With over 50,000 controls

•  Secondary use of data is likely to be valuable –  Precedent from WT-‐CCC


Yesterday…

hdp://www.broadinsEtute.org/news/5896

Cases: 34,241 Controls: 45,604 Trios: 1,235


Why is informaEcs important? What will GeL contribute?

•  Widely acknowledged that informaEcs, not sequencing, is rate limiEng in genomics research

•  GeL addresses informaEcs problems that will become rouEne in a few years; –  TranslaEon of academic bioinformaEcs technologies into clinical

se{ngs –  Development of new approaches for disease research

•  PotenEal to reach beyond immediate GeL focus of cancer and rare inherited disorders

•  Creates new markets for genomics data; disrupEve technology –  E.g. PotenEal to adract clinical trials back to the UK


Eagle® is a registered trademark no. 010418135 of Eagle Genomics Ltd. Postal address: Eagle Genomics Ltd., Babraham Research Campus, Cambridge CB22 3AT, United Kingdom.


[email protected] +44 (0)1223 654481 www.eaglegenomics.com

facebook.com/eaglegenomics blog.eaglegenomics.com @wspoonr @eaglegen

will spooner - big data in mental health - 23rd july 2014

Health & Medicine