CityAge: The Data Effect Vancouver

1. My
Personal
Odyssey
with
Big
Data
Brad
Popovich
Chief
Scien2fic
Officer
December
5,
2013

2. The
early
days
of
exploring
my
personal
genome
• 1976:
My
first
whole
genome
analysis
(46
XY)
• 1980-­‐2000:
I
looked
at
almost
every
gene
I
could
in
my
personal
genome
for
CFTR,
FMR1,
DMD,
DM,
HD,
SCA,
SMA,
MELAS,
MERRF,
etc.
• LiUle
concern
personally
• ExcepWon:
APOE
2

3. 3
3

4. My
early
concern:
Demen<a
• PosiWve
family
history:
• Increase
life
Wme
risk
(20-­‐25%
vs.
10%)
• APOE
• e4/e4:
further
increase
in
risk
• Good
news:
• APP
(2012)
protecWve
mutaWon
(A673T)
4

5. 2013-­‐2014:
My
personal
Whole
Genome
Sequence
(WGS)
Logical
next
step
• It’s
my
personal
“blue
print”
• Provides
potenWal
for
informed
decision
making
• It’s
accessible
• Learn
the
difference
between
talking
about
genomics
vs.
being
a
consumer
5

6. Consumer
driven
genomics
WGS
2007:
First
offered
by
Knome
($350k)
2009:
Illumina
($45k)
2013:
TesWng
now
offered
by
several
labs/
companies
for
approximately
$5k
Genotyping
tesWng
available
from
several
labs/
companies
(e.g.
23andMe
@
$99)
• FDA
(November
2013)
• Class
acWon
suit
(December
2013)
6

7. Obtaining
my
personal
WGS
Presently
several
opWons
for
WGS
Illumina:
Understand
Your
Genome
(UYG)
• Physician
referral
required
• Reason
for
my
referral:
General
medical
knowledge
-­‐
not
for
any
specific
medical
quesWon
• DNA
sequence
generated
in
CAP/CLIA
accredited
lab
• UYG
Course
in
March
2014
• Sokware
tool
provided:
MyGenome
App
• App
allows
future
genomic
interrogaWon
7

8. FDA
Approval:
November
19,
2013
• For
the
first
Wme,
the
U.S.
Food
and
Drug
AdministraWon
has
cleared
a
next-­‐
generaWon
sequencer
for
use
in
clinical
laboratories,
advancing
the
use
of
genomic
medicine
in
rouWne
medical
care.
• Francis
Collins
(NEJM):
"The
markeWng
authorizaWon
for
the
first
next-­‐generaWon
genome
sequencer
represents
a
significant
step
forward
in
the
ability
to
generate
genomic
informaWon
that
will
ulWmately
improve
paWent
care.
The
availability
of
high-­‐throughput
DNA
sequencers
will
enable
physicians
to
take
a
comprehensive
look
at
a
paWent's
geneWc
blueprint,
or
genome,
to
search
for
a
wide
range
of
variaWons
or
changes
that
increase
risk
of
disease,
drive
the
disease
process,
and/or
affect
response
to
medicaWons
and
other
treatments.
Such
informaWon
has
the
potenWal
to
benefit
paWents
in
many
ways.
This
acWon
reflects
our
naWon's
commitment
to
a
future
in
which
health-­‐care
professionals
will
be
able
to
use
each
person's
unique
genome”
• FDA
also
approved
the
first
test
system
based
on
two
devices
-­‐
the
Illumina
MiSeqDx
instrument
and
the
reagents
in
the
Illumina
Universal
Kit
-­‐
to
allow
laboratories
to
develop
and
validate
sequencing
of
any
part
of
the
paWent's
8
genome.

9. Whole
Genome
Sequence
(WGS)
Few
technical
barriers
•
• ApplicaWons
• Primarily
a
research
tool
• Clinically:
cancer,
infecWous
diseases,
and
difficult
to
diagnosis
diseases
• Difference
between
WGS,
exome
and
targeted
gene
panel
approaches
• Size
of
corresponding
data
sets
for
human
• WGS
3x109
bp
(file
size
Gb
–
Mb)
• Exome
=
3x107
bp
(approx
1%
of
WGS)
• BoUleneck…interpreWng
the
data
9

10. Interpre<ng
Whole
Genome
Sequence
Necessary
to
know
• What’s
normal
vs.
a
variant
across
the
enWre
genome
• Phenotypic
consequences
of
normal
vs.
variant
genotype
Current
barriers
• Size
of
human
cohorts
available
for
comparison
• Lack
of
staWsWcal
power
to
validate
research
findings
• Quality
of
phenotypic
data
• Lack
of
adequate
EMR,
data
standards,
QA,
and
QC
Ideal
clinical
applicaWons
• Allow
normal
vs.
abnormal
comparison
in
the
same
10
paWent
(e.g.
cancer)

11. What
do
I
expect
to
learn
from
my
WGS?
• What
being
a
consumer
of
genomic
informaWon
feels
like
• Some
detected
variants
will
cause
concern
• Will
the
HC
system
accommodate
medically
acWonable
follow-­‐up?
• Most
variants
will
lack
the
necessary
data
to
have
clinical
uWlity
• How
can
we
move
from
variants
of
unknown
significance
to
significant?
• What’s
the
impact
of
waiWng?
11
• Can
apps
ease
the
burden
on
the
system?

12. What
do
I
expect
to
learn
from
my
WGS?
(Con<nued)
• Family
maUers
• Modified
risk
for
demenWa
• CommunicaWons
with
family
members
• Impacts
on
my
insurability
• Life
• Disability
• What
professional
support
will
be
required?
12

13. Genome
BC
and
WGS
• Many
of
the
projects
funded
by
Genome
BC
are
already
performing
WGS
on
research
subjects
• I
anWcipate
that
in
the
near
future
most
projects
on
humans
will
be
using
WGS
or
WES
• ObservaWon:
ASHG
and
AMP
2013
13

14. Genome
Bri<sh
Columbia
and
WGS
What
is
the
role
of
Genome
BC
in
making
WGS
clinically
useful
and
cost
effecWve?
• Stop
geneWc
/
genomic
excepWonalism
• Coordinate
the
large-­‐scale
collecWon
of
genomic
data
in
a
manner
that
addresses
privacy
and
confidenWality
• Develop
strong
baseline
protecWons
for
parWcipants
in
clinical
and/or
research
applicaWons
of
WGS
• Promote
data
access
and
sharing
• Develop
standards
for
the
integraWon
of
genomic
informaWon
into
health
records
• Facilitate
access
to
genomic
informaWon
so
all
BriWsh
14
Columbians
benefit

15. What’s
missing?
A
plan!
• R&D
• ComputaWonal
infrastructure
• Privacy
policy/law
• Access
policy
• Pla{orms
• Data
repository
• Clinical
implementaWon
• Medical
evidence
and
health
economic
data
• Linkage
of
genomic
data
into
HC
records
• Improved
receptor
capacity
• Physicians,
geneWc
counselors,
apps,
etc.
15

16. Applica<ons
Human
• Cancer
• InfecWous
diseases
• Difficult
to
diagnose
diseases
• Pharmacogenomics
• Forensics
• Public
health
• Newborn
screening
Non-­‐human
• Forestry
• Fisheries
• Environmental
monitoring
• Agri-­‐Food
Industry
• Mining
16

17. Conclusions
• I
am
about
to
conclude
an
important
chapter
in
my
genomic
odyssey
• I
plan
to
use
my
experience
to
inform
the
work
that
Genome
BC
is
doing
to
make
this
technology
accessible,
useful,
and
economically
viable
to
the
ciWzens
of
BC,
Canada,
and
beyond
• We
need
to
end
geneWc
excepWonalism
• We
need
leadership
and
a
plan!
17