The document describes the UK 100,000 Genomes Project, which aims to sequence 100,000 genomes from NHS patients by 2017. It will provide benefits to patients through new treatments and insights, contribute to the UK economy through commercial activity in genomics, and help integrate genomic medicine into clinical practice in the NHS. Genomics England was established to lead the project and work with partners including NHS England, 11 Genomic Medicine Centres, and commercial companies. The project involves genome sequencing, analysis, and returning results to clinicians to inform treatment.

1.
www.genomicsengland.co.uk
The
UK
100,000
Genomes
Project
February
2015

2. 2
The
100,000
Genomes
Project
Announced
by
the
Prime
Minister
in
December
2012
An
Olympic
Legacy
Genomics
England
announced
by
Secretary
of
State
for
Health
in
speech
during
NHS
65th
Anniversary
CelebraKons,
July
2013

3. 3
Why
are
we
doing
this?
Three
major
legacies
for
pa?ents,
the
NHS
and
the
UK
economy
by
2017
Increased
insight
and
understanding
leading
to
new
treatments,
devices
and
diagnos?cs
Thriving
private
sector
investment
and
commercial
acKvity
in
genomics
Advanced
genomic
medicine
pracKce
integrated
into
the
NHS
Plus
Posi?ve
Public
Support

4. 4
Data
Type
Large-­‐scale
Structural
Changes
Balanced
Transloca?ons
Distant
Consanguinity
Uniparental
Disomy
Novel
/
Known
Coding
Variants
Novel
/
Known
Non-­‐coding
Variants
Targeted
gene
sequencing
û û û û ü û
SNP+
arrays
ûü û ü ü û û
Array
CGH*
ûü û û û û û
Exome
ûü û ûü ûü ü û
Whole
Genome
ûü ü ü ü ü ü
+
Single
NucleoKde
Polymorphism
*
ComparaKve
Genomic
HybridisaKon
Whole
genome
sequencing
will
give
us
new
insights
10,000
100,000
1,000,000
10,000,000
100,000,000
1,000,000,000
10,000,000,000
0
0.5
1
1.5
2
2.5
Genotyping
Whole
genome
3.3bn
bases
Both
exons
and
introns
Exome
10m
bases
Exons
only
Panels
<10m
bases
Subset
of
exons

5. 5
Key
Opera?onal
Features
} Structurally
integrated
with
Na?onal
Health
Service
} Selected
pa?ent
cohort
with
common
cancers
and
rare
inherited
diseases
} PaKents
posiKvely
consent
} Sequencing
is
undertaken
in
new
state-­‐
of-­‐the-­‐art
sequencing
centre
} Data
is
held
in
a
safe
haven
with
strictly
regulated
access
to
ensure
public
confidence
} Very
large
number
of
scienKsts
and
clinicians
engage
through
disease
based
Clinical
Interpreta?on
Partnerships
} Commercial
companies
will
have
defined
routes
to
access
} Common
pool
of
Intellectual
Property
held
by
Genomics
England
and
available
for
licence
} Genomic
medicine
educa?on
programme
is
mounted
in
the
NHS
to
prepare
for
feedback
} Genomics
England
is
consKtuted
as
a
limited
company
under
the
governance
of
a
board
with
a
majority
of
independent
directors
to
enable
the
agility
necessary
to
lead
in
this
fast
developing
field

6. 6
Key
Pillars
for
Public
Support
} Structurally
integrated
with
Na?onal
Health
Service
} Selected
pa?ent
cohort
with
common
cancers
and
rare
inherited
diseases
} PaKents
posiKvely
consent
} Sequencing
is
undertaken
in
new
state-­‐
of-­‐the-­‐art
sequencing
centre
} Data
is
held
in
a
safe
haven
with
strictly
regulated
access
to
ensure
public
confidence
} Very
large
number
of
scienKsts
and
clinicians
engage
through
disease
based
Clinical
Interpreta?on
Partnerships
} Commercial
companies
will
have
defined
routes
to
access
} Common
pool
of
Intellectual
Property
held
by
Genomics
England
and
available
for
licence
} Genomic
medicine
educa?on
programme
is
mounted
in
the
NHS
to
prepare
for
feedback
} Genomics
England
is
consKtuted
as
a
limited
company
under
the
governance
of
a
board
with
a
majority
of
independent
directors
to
enable
the
agility
necessary
to
lead
in
this
fast
developing
field

7. 7
Consent
&
Sample
collecKon
DNA
extracKon
Biorepository
Sequencing
Variant
Calling
InterpretaKon
Feedback
to
clinician
ValidaKon
Treatment
Clinical
Data
To
complete
the
Treatment
Cycle
for
just
one
Pa?ent
requires
a
Complex
Chain
of
Opera?ons
involving
numerous
Specialist
Resources
And
most
of
these
operaKons
have
not
been
designed
or
opKmised
for
the
purposes
of
Genomic
Medicine.
So
the
task
is
truly
one
of
iniKaKng
a
TransformaKon
in
Medical
PracKce,
parKcularly
relaKng
to
rouKne
use
of
coordinated
data.

8. 8
This
Project
is
far
too
Big
and
Complex
to
be
undertaken
by
a
Single
Organisa?on
NHSE
and
GMCs
GeCIPs
Commercial
Partnerships
Genomics
England
The
Principal
Partners
Illumina

9. 9
Clinical
Partnership
• NHS
England
is
responsible
for
the
medical
care
of
53
million
people
• In
their
recent
strategy
document
NHS
England
have
put
Genomic
Medicine
in
the
centre
of
their
vision
of
future
medical
pracKce
• As
first
step
NHS
England
have
run
a
naKon-­‐wide
compeKKon
to
select
11
Genomics
Medicine
Centres
(GMCs)
to
coordinate
and
integrate
the
work
of
more
than
100
Hospital
Trusts
o IdenKfying
and
recruiKng
paKents
matching
the
project
requirements
o Obtaining
informed
consent
o Obtaining,
storing
and
transporKng
blood
samples
o Obtaining,
fixing,
storing
and
transporKng
biopsies
and
resecKons
o Where
appropriate
extracKng
tumour
cell
samples
o Providing
first
dataset
necessary
for
sequencing
o Providing
clinical
dataset
necessary
for
analysis
o Receiving
and
validaKng
the
clinical
feedback
o Informing
and
treaKng
the
paKents
Consent
&
Sample
collecKon
DNA
extracKon
Biorepository
Sequencing
Variant
Calling
InterpretaKon
Feedback
to
clinician
ValidaKon
Treatment
GMC
responsibility
• GMCs
will
be
the
focal
points
for
coordinaKng
the
supply
of
samples
and
data
for
their
region
and
receiving
the
clinical
feedback
and
will
be
responsible
for
(amongst
other
things)

10. 10
Sequencing
Partnership
• We
ran
a
worldwide
compeKKon
open
to
any
provider
who
could
demonstrate
an
ability
to
provide
accurate
whole
genome
sequences
• Chose
Illumina
as
the
best
demonstrable
product,
the
clearest
understanding
of
the
requirement,
and
the
most
complete
offering
• Signed
a
Partnership
agreement
in
July
2014
o Illumina
invest
in
a
state-­‐of-­‐the-­‐art
sequencing
centre
at
Hinxton
o Wellcome
Trust/Sanger
provide
the
physical
infrastructure
o Illumina
are
commifed
to
working
with
us
to
opKmise
the
genomics
medicine
cycle
from
receipt
of
the
DNA
through
to
interpretaKon
and
to
advise
on
the
protocols
in
the
clinical
pathways
to
maximise
the
probability
of
reliable
and
Kmely
results
Consent
&
Sample
collecKon
DNA
extracKon
Biorepository
Sequencing
Variant
Calling
InterpretaKon
Feedback
to
clinician
ValidaKon
Treatment

11. 11
Clinical
Interpreta?on
Partnerships
• We
ran
a
world-­‐wide
compeKKon
to
test
the
state-­‐of-­‐the-­‐art
in
annotaKon
and
interpretaKon
of
genomic
data
• It
is
clear
that
scienKfic
and
clinical
understanding
is
far
from
mature
• So
we
have
iniKated
the
creaKon
of
a
network
to
draw
in
the
best
clinical
and
scienKfic
minds
from
the
UK
and
around
the
world
to
access
our
data
and
interpret
the
results
Sample
collecKon
DNA
extracKon
Biorepository
Sequencing
Variant
Calling
InterpretaKon
Feedback
to
clinician
ValidaKon
Treatment
Work
of
~40
disease
groups
involving
upwards
of
1000
Clinicians
and
ScienKsts
The
Genomics
England
Clinical
InterpretaKon
Partnerships
are
• Defined
by
diseases
or
cross
cujng
themes.
We
expect
40+
GeCIPs
in
all
• Each
must
have
a
clear
and
unique
focus
and
be
open
to
all
experts
in
that
field.
We
expect
an
average
of
maybe
50
• Once
designated
GeCIPs
have
free
access
to
the
data
infrastructure
and
the
dataset
• All
IP
held
by
Genomics
England
but
available
for
licence

12. 12
Genomics
England
specific
Responsibili?es
Sequencing
Centres
Biorepository
Consent
Clinical
Data
Samples
Samples
Samples
Clinician
Genomics
England
InformaKcs
Infrastructure
ScienKfic
+
Clinical
Users
Commercial
Users

13. 13
InformaKcs
Architecture
Fast
Track
Feedback
Path
Data
Handling
Cohort
Handling
Variant
Calling
+++
+++
M
Clinical
Data
IdenKty
Data
Clinical
Data
VCFs
BAMs
• Management
• Genomic
data
checking
• User
idenKty
checking
• Resource
allocaKon
• AcKvity
oversight
• Output
report
validaKon
Management,
QC,
IdenKty
control,
Clinical
feedback
GeCIP
embassies
Commercial
embassies
Clinical
Feedback
Report
From
GMCs
From
Sequencing
Centre
InterpretaKon

14. 14
Commercial
Partnerships
Ø For
the
Pharma
industry
we
are
proposing
they
join
a
pre-­‐compeKKve
consorKum
and
engage
in
an
iniKal
trial
using
a
set
of
5000
genomes
together
with
appropriate
clinical
data
Ø For
the
Biotech
industry
we
will
configure
more
focused
datasets
for
a
trial
period
to
give
each
access
to
data
relevant
to
their
business
plan
Ø For
the
Bio-­‐informa?cs
and
Analy?cs
industry
we
will
choose
the
best
performing
players
to
work
with
us
as
Plalorm
Partners
to
prove
their
techniques
and
tools
and
provide
clinical
interpretaKon
and
services
to
our
research
customers
We
have
segmented
the
space
into
three
broad
categories
with
a
different
approach
to
each

15. 15
But
there
are
many
other
Important
Partnerships
Ø Precursor
Rare
Disease
Programmes:
Oxford’s
WGS500
project,
the
Sanger’s
Deciphering
Developmental
Disorders
project,
and
NIHR’s
Bioresource
Rare
Disease
project
are
all
precursors
which
are
both
providing
invaluable
learning
and
also
addiKonal
input
to
our
dataset
Ø Mul?-­‐omics
approach
to
Cancer:
we
are
working
with
Oxford
University’s
Chan-­‐Soon-­‐Shiong
Oxford
Centre
for
Molecular
Medicine
and
Nanthealth
to
opKmise
Kssue
sample
techniques
and
use
mulK-­‐omics
processes
for
providing
individualised,
data
driven
molecular
based
medicine
Ø Molecular
Pathology:
we
are
working
with
iniKaKves
launched
by
the
MRC
and
the
Royal
College
of
Pathologists
to
examine
improvements
in
protocols
and
equipment
to
enhance
quality
of
DNA,
parKcularly
for
cancer
tumours
Ø Longitudinal
Clinical
Data:
our
consent
protocol
permits
revisits
and
data
refresh
up
to
4
Kmes
per
annum
Ø Circula?ng
Tumour
Cells:
we
have
a
number
of
partners
interested
in
opKmising
techniques
for
extracKng
quality
tumour
DNA
in
circulaKon
so
as
to
understand
progression
of
cancer
To
deliver
the
ambiKons
of
this
project
we
are
working
with
other
key
partners
to
address
numerous
related
issues.
These
include

16. 16
Where are we on our plan?
Phase
2
-­‐
Pilots
Phase
3a
–
Main
Programme
Proving
Phase
Phase
3b
–
Main
Programme
Running
at
Volume
Phase
1
Bake-­‐offs
0
10000
20000
30000
40000
50000
60000
2014
2015
2016
2017
Genomes
per
Annum
So
what
have
we
achieved
so
far?
Ø Bake-­‐offs
to
establish
state-­‐of-­‐the-­‐art
Ø Completed
vigorously
contested
compeKKve
process
resulKng
in
very
producKve
partnership
relaKonship
with
Illumina
Ø Pilots
almost
completed
Ø 2000+
sequences
being
loaded
into
data
system,
plus
another
1000
completed
(to
be
delivered
later)
Ø Extra
cancer
programme
underway
to
opKmise
cancer
tumour
DNA
extracKon
Ø Pilot
clinical
data
capture
tool
operaKng
in
cancer
pilot
Ø Many
lessons
learned
concerning
opKmising
clinical
processes
Ø First
implementaKon
of
informaKcs
infrastructure
went
live
end
of
January
Ø Clinical
data
capture
tool
roll
out
end
of
January
Ø GMCs
mobilisaKon
due
February
Ø GeCIP
programme
launched,
proposals
under
consideraKon
Ø IniKal
commercial
model
being
trialled,
pharma
and
biotech
companies
being
signed
up
Ø Phenomenal
world
wide
interest
in
the
programme

17. 17
What
can
we
expect
from
this
Project?
Ø Feedback
on
perKnent
findings
–
which
will
get
quicker
and
befer
informed
as
the
project
progresses
Ø If
the
paKent
opts
for
it,
feedback
on
any
high
probability
pathogenic
findings
–
again
this
will
develop
as
the
project
progresses
Ø Access
under
strict
governance
rules
to
the
increasing
dataset
and
a
suite
of
best
in
class
tools
Ø Engagement
in
a
collaboraKve
programme
with
leading
scienKfic
and
clinical
experts
Ø Opportunity
to
share
in
the
publicaKon
of
findings
Ø Possibility
to
engage
in
translaKon
opportuniKes
with
commercial
collaborators
PaKents
Research
Collaborators

18. 18
What
can
we
expect
from
this
Project?
Ø A
number
of
mechanisms
to
gain
access
to
the
dataset
and
tools
under
strict
governance
rules
Ø Engagement
with
the
research
collaborators
and
access
to
expert
clinical
and
bio-­‐informaKcs
support
Ø Opportunity
to
address
relevant
paKent
cohorts
both
through
the
Genomics
England
dataset
and
through
other
UK
collaboraKons
Ø Opportunity
to
take
up
licences
to
commercialise
findings
Ø Possibility
of
significant
advances
in
diagnosKc
markers
of
geneKc
diseases
Ø Possibility
of
new
understanding
of
mutaKons
causing
progress
of
common
cancers
Ø Possibility
of
fresh
insights
into
geneKc
markers
for
common
diseases
Commercial
Companies
General
Public

19. 19
By
achieving
these
we
will
deliver
the
legacies
Increased
insight
and
understanding
leading
to
new
treatments,
devices
and
diagnos?cs
Thriving
private
sector
investment
and
commercial
acKvity
in
genomics
Advanced
genomic
medicine
pracKce
integrated
into
the
NHS
ü
ü
üPlus
Posi?ve
Public
Support
ü