Phase 1 Phase 2 Phase 3 Approval Cumulative

Pe

rce

nt

su

cce

ss

020

40

60

80

10

0

15%

Drug development rarely succeeds

Hay et al. Nature Biotechnology. 2014.

Human genetics can help

Nelson et al. Nature Genetics. 2015.

Industrializing big data integrationHuman genetics & human cells

A new type of partnership

Industrializing data integration

GWAS COSMIC

OMIM/ClinVar

ExAC

United data model, pathways, statistical

integration, ENSEMBL regulatory build

Biopsies Crypt

isolation Organoid culture

QC Experiments Data

analysis

Set up stage Development stage Analysis

Freeze/Storage

Phenotyping qPCR/

imaging

Expansion

IL22 stimulation

Archiving

infection

Microbiota

Genotyping

Proteomics

Transcriptomics

Methylation

Workflow for Establishing Organoid Bank

In collaboration with Matt Zilbauer

Human genetics & human cells

IBD, combined phenotype (Nov 2012)

Chromosome 18 (kb)

44500 44600 44700 44800 44900

0

2

4

6

8

Observ

ed (

−lo

gP

)

0

20

40R

ecom

bin

ation r

ate

(cM

/Mb

)p = 5.0e−08

rs7240004 (P = 6.1e−06)

1 0.8 0.6 0.4 0.2

1 . rs7240004 : Inflammatory_bowel_disease(1E−9)

11

2 . rs4939827 : Colorectal_cancer(8E−28)

22

3 . rs357894 : Dental_car ies(4E−6)

33

4 . rs1787200 : Height(1E−10)

44

rs7240004, incl. replication (P = 9.81e−09)

KIAA0427

SMAD7

DYM

DNA/RNA products

ChIP training

A new type of partnership