This document discusses the need for a framework to extract clinical value from the large amount of genomic data generated by next generation sequencing (NGS). While NGS has exponentially increased sequencing output over time, there remains a challenge in translating this genomic data into clinically useful knowledge. The document proposes viewing the clinical translation process as analogous to a manufacturing plant, and emphasizes that sequencing output, IT processing capabilities, human expertise, molecular biology knowledge, and various bioinformatics tools must be integrated to transform genomic data into clinically applicable knowledge.

1. Extrac'ng
Clinical
Value
from
Next
Gen
Sequencing
(NGS)
Frameworks
for
the
Transforma'on
to
Medical
Knowledge

2. A
Framework
Needed
to
Extract
Clinical
Value
from
the
Overabundant
Data
from
NGS
• Since
before
the
human
genome
project
was
completed,
the
throughput
of
nucleic
acid
sequencing
has
grown
exponen'ally
over
'me,
and
resul'ng
costs
exponen'ally
decline.
• This
situa'on
has
only
grown
more
acute
since
the
introduc'on
of
next
gen
sequencing.
• The
conundrum
is
how
to
translate
or
transform
the
overabundance
of
genomic
data
into
clinically
useful
knowledge.
©
2013
Winton
Gibbons
2

3. Genomic
Data
from
NGS
Requires
Transforma'on
to
be
Used
Clinically
Data
Raw
sequence
Informa+on
Assembled
and
annotated
data
Knowledge
Informa'on
applied
to
par'cular
purpose
©
2013
Winton
Gibbons
3

4. Follow
the
WIP
as
much
as
the
Money
• To
iden'fy
leverage
|
pressure
points—presen'ng
both
opportuni'es
and
problems—the
NGS
clinical
transla'on
process
should
be
viewed
as
analogous
to
a
manufacturing
plant.
• For
opportuni'es
or
leverage
points,
follow
the
WIP
(work
in
process).
Where
there
is
too
much,
downstream
capacity
is
required,
or
a
new
“machine”
need
to
convert
the
WIP:
oen
new
soware,
but
can
be
new
instrumenta'on,
or
even
clinical
data.
• At
any
point
in
'me,
there
will
be
over-­‐and
under
capacity
for
various
stages,
e.g.,
too
much
raw
sequence
data
|
too
few
assembled
genomes
|
fewer
clinical
databases
|
yet
fewer
transla'onally
trained
doctors
|
insufficient
integra'on
among
gene'cs,
drugs
and
regulatory.
• Different
vendors
and
users
will
likely
be
honed
for
various
steps
in
the
process,
not
fully
integrated.
Some
may
choose
to
integrate,
but
that
is
likely
best
done
through
acquisi'on
of
the
best-­‐of-­‐breed.
• The
balance
will
not
always
stay
the
same.
It
is
likely
there
will
yet
be
an
oversupply
(not
just
overproduc'on)
of
sequencing
capacity.
Sequencer
and
reagent
growth
might
stall.
Clinical
databases
will
catch
up
for
some
condi'ons,
and
not
for
others.
For
some
medical
special'es,
use
of
gene'cs
will
come
before
it
does
for
others.
Regulatory
and
reimbursement
will
lag.
©
2013
Winton
Gibbons
4

5. There
are
Three
Core
Resources
and
Capabili'es
for
this
Transforma'on
©
2013
Winton
Gibbons
5
Sequencing
output
IT
processing
throughput
Human
exper'se

6. Molecular
Biology
Complements
this
Core
©
2013
Winton
Gibbons
6
Genomic
sequencing
Puta've
muta'ons
Proteins
or
epigene'cs
Func'on
Clinical
effect
Sequencing
output
IT
process
ing
throug
hput
Human
exper's
e

7. And
a
Number
of
IT
Plaeorms/Algorithms
Facilitate
the
Transforma'on
©
2013
Winton
Gibbons
7
Genome
assembly
Computa'onal
comparison
and
annota'on
Visualiza'on
Experimental
planning
and
data
collec'on
Desktop
integra'on,
and
Soware
as
a
Service
(SaaC)
Genomi
c
sequenc
ing
Puta've
muta'o
ns
Proteins
or
epigene
'cs
Func'o
n
Clinical
effect
Sequencin
g
output
IT
proce
ssing
throu
ghput
Human
exper'
se

8. Only
with
the
Integrated
Aspects
Outlined
will
the
Abundance
of
NGS
Data
Contribute
Clinically
Data
Raw
sequence
Informa+on
Assembled
and
annotated
data
Knowledge
Informa'on
applied
to
par'cular
purpose
©
2013
Winton
Gibbons
8
• Integrate
medical
condi'on
with
informa'on
on
gene'c
varia'on,
and
protein
func'on.
• Provide
through
a
user-­‐friendly
query
and
visualiza'on
interface.

9. • LinkedIn
– hkp://www.linkedin.com/in/wintongibbons/
• Twiker
– @wingibbons
• Blog
– hkp://www.wingibbons.wordpress.com
©
2013
Winton
Gibbons