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clearScienceStrataRx2012
1. clear Science
dragging scientific communication into
the information age
erich s. huang, md/phd
director, cancer research
sage bionetworks
erich.huang@sagebase.org
@erichhuang
3. Betty Jones
“I have a lump near my mastectomy scar”
4. Betty Jones
menopause
~50 years
“high risk” breast cancer “normal risk” breast cancer
5. Betty Jones
menopause
36 years ~50 years
“high risk” breast cancer “normal risk” breast cancer
6. Betty Jones
African American Population Non-African American Population
16%
39%
61%
84%
Triple Negative Breast Cancer Triple Negative Breast Cancer
All Other Types All Other Types
http://jama.jamanetwork.com/article.aspx?articleid=202952
7. her2
receptor
progesterone
receptor
estrogen
receptor
breast cancer cell
depends on receptor-driven
growth signals
8. her2
receptor
progesterone
receptor
estrogen
receptor
breast cancer cell
depends on receptor-driven
growth signals
9. her2
receptor
progesterone
receptor
LS
estrogen
NA
receptor
S IG
T H
OW
G R
breast cancer cell
depends on receptor-driven
growth signals
11. “triple negative” breast cancer
breast cancer cell
growth signals become
independent of receptors
12. “triple negative” breast cancer
the receptors are no longer present on the
cell surface...
breast cancer cell
growth signals become
independent of receptors
13. “triple negative” breast cancer
the receptors are no longer present on the
cell surface...
but the intracellular signals persist
breast cancer cell
growth signals become
independent of receptors
14. “triple negative” breast cancer
the receptors are no longer present on the
cell surface...
but the intracellular signals persist
T
N S
E L
D A
N N
E IG
EP S
D H
IN T
OW
G R
breast cancer cell
growth signals become
independent of receptors
21. radiotherapy 3d planning
http://radonc.ucsf.edu/patient_information/breast/images/Radiation_Oncology_breast_img_2.jpg
22. Betty Jones
“I have a lump near my mastectomy scar”
23. Betty Jones
Triple negative breast cancer.
What are the options?
24. Betty Jones
Triple negative breast cancer.
What are the options?
Standard Stuff (Old Fashioned Targets)
Anthracyclines
Taxanes
Anti-Metabolites
25. Betty Jones
Triple negative breast cancer.
What are the options?
Standard Stuff (Old Fashioned Targets)
Anthracyclines
Taxanes
Anti-Metabolites
Platinum Agents
26. Betty Jones
Triple negative breast cancer.
What are the options?
{
Standard Stuff (Old Fashioned Targets)
Anthracyclines
conventional Taxanes
chemotherapy Anti-Metabolites
Platinum Agents
27. Betty Jones
Triple negative breast cancer.
What are the options?
{
Standard Stuff (Old Fashioned Targets)
Anthracyclines
conventional Taxanes
chemotherapy Anti-Metabolites
Platinum Agents
Targeted Agents
Cetuximab + Platinum (BALI-1)
Bevacizumab (GeparQuinto)
PARP Inhibitors
SRC Inhibitors
HDAC Inhibitors (ER-alpha)
28. Betty Jones
Triple negative breast cancer.
What are the options?
{
Standard Stuff (Old Fashioned Targets)
Anthracyclines
conventional Taxanes
chemotherapy Anti-Metabolites
Platinum Agents
{
Targeted Agents
Cetuximab + Platinum (BALI-1)
Bevacizumab (GeparQuinto)
new therapies PARP Inhibitors
SRC Inhibitors
HDAC Inhibitors (ER-alpha)
29. Betty Jones
Triple negative breast cancer.
What are the options?
{
Standard Stuff (Old Fashioned Targets)
Anthracyclines
conventional Taxanes
chemotherapy Anti-Metabolites
CURRENT KNOWLEDGE:
Platinum Agents
ALL THESE THERAPIES
{
Targeted Agents
ARE A Platinum (BALI-1)
Cetuximab + WASH
Bevacizumab (GeparQuinto)
new therapies PARP Inhibitors
SRC Inhibitors
HDAC Inhibitors (ER-alpha)
63. the status quo can reproduce
tolerates poor partially
communication
of findings
6%
can reproduce
from processed
data w/ 21%
discrepancies
54%
can reproduce w/ 8% cannot
discrepancies reproduce
11%
can reproduce in
principle
65. so what’s in
principle
208,294,724
reproducible, is not
datapoints practically
reproducible
124 pages
supplemental material
? lines
unobtainable source
code
? version or
architecture of R
? R packages
key R package
“ClaNC”
no longer
available
442 citations
69. THE SCIENTIFIC PROCESS:
it’s not one and done...
define a question form a hypothesis
gather information experimentally test
your hypothesis
70. THE SCIENTIFIC PROCESS:
it’s not one and done...
analyze
define a question form a hypothesis experimental data
gather information experimentally test
your hypothesis
71. THE SCIENTIFIC PROCESS:
it’s not one and done...
analyze
define a question form a hypothesis experimental data
gather information experimentally test draw conclusions
your hypothesis
72. THE SCIENTIFIC PROCESS:
it’s not one and done...
analyze
define a question form a hypothesis experimental data report, i.e. “publish”
gather information experimentally test draw conclusions
your hypothesis
73. THE SCIENTIFIC PROCESS:
it’s not one and done...
analyze
define a question form a hypothesis experimental data report, i.e. “publish”
gather information experimentally test draw conclusions
your hypothesis
validation by the scientific community
validation by clinical trials
79. store on local
generate data server
@ the bench or
from a clinical cohort
analyze on local
machine
80. store on local
generate data server
@ the bench or
from a clinical cohort
analyze on local
machine
81. store on local
generate data server
@ the bench or
from a clinical cohort
analyze on local
machine
write a
document
82. store on local
generate data server
@ the bench or
from a clinical cohort
analyze on local
machine
write a
document
al
to journ
su bmit
83. store on local
generate data server
@ the bench or
from a clinical cohort
analyze on local
machine
sent to
write a reviewers
document as pdf
al
to journ
su bmit
84. store on local
generate data server
@ the bench or
from a clinical cohort
analyze on local
machine
sent to
write a reviewers
document as pdf
al
to journ
su bmit
85. store on local
generate data server
@ the bench or
from a clinical cohort
accepted
& digitally
typeset
analyze on local
machine
sent to
write a reviewers
document as pdf
al
to journ
su bmit
86. printed
on paper
store on local
generate data server
@ the bench or
from a clinical cohort
accepted
& digitally
typeset
analyze on local
machine
sent to
write a reviewers
document as pdf
al
to journ
su bmit
87. printed
on paper
store on local
generate data server
@ the bench or
from a clinical cohort static html
representation
accepted
& digitally
typeset
analyze on local
machine
sent to
write a reviewers
document as pdf
al
to journ
su bmit
88. printed
on paper
store on local
generate data server
@ the bench or
from a clinical cohort static html
representation
accepted
& digitally
typeset
static pdf
representation
analyze on local
machine
sent to
write a reviewers
document as pdf
al
to journ
su bmit
89. printed
on paper
store on local
generate data server
@ the bench or
from a clinical cohort static html
representation
accepted
& digitally
typeset
static pdf
representation
analyze on local
machine
sent to
write a reviewers
document as pdf
al
to journ
su bmit
90. printed
on paper
store on local
generate data server
@ the bench or
from a clinical cohort static html
representation
THE ACTUAL SCIENCE accepted
& digitally
typeset
static pdf
representation
analyze on local
machine
sent to
write a reviewers
document as pdf
al
to journ
su bmit
91. printed
on paper
store on local
generate data server
@ the bench or
from a clinical cohort static html
representation
THE ACTUAL SCIENCE accepted
& digitally
typeset
static pdf
representation
analyze on local
machine
SCIENTIFIC CLAIMS
sent to
write a reviewers
document as pdf
al
to journ
su bmit
92. store on local
generate data server
@ the bench or
from a clinical cohort
THE ACTUAL SCIENCE
analyze on local
machine
93. store on local
generate data server
@ the bench or
from a clinical cohort
THE ACTUAL SCIENCE
analyze on local
machine
99. clear Science
1. re-imagine scientific communication
2. make every component of a data-intensive project
(e.g. genomic analysis) web accessible
100. clear Science
1. re-imagine scientific communication
2. make every component of a data-intensive project
(e.g. genomic analysis) web accessible
3. allow consumption of content at a variety of levels
of complexity and abstraction
4. leverage open, RESTful APIs
109. code
data
software
hardware
clear Science
a narrative that coherently interweaves
scientific assertions with the executable data,
code, software & hardware that support them
113. “ If I have seen further it is by standing on the shoulders
of giants. ”
114. Betty Jones
“I have a lump near my mastectomy scar”
115.
116. brian bot
stephen friend
josh greenberg david burdick
mike kellen
external partners
myles axton ian mulvaney kelly lamarco
editor head of technology senior editor
nature genetics •
science trans. medicine
mark patterson
managing exec. editor
phil bourne eLife sciences eric schadt
founding editor-in-chief dir. inst. for genomics &
plos comp. biology multiscale biology
mt. sinai school of med.
117. brian bot
stephen friend
josh greenberg david burdick
mike kellen
our patients
external partners
myles axton ian mulvaney kelly lamarco
editor head of technology senior editor
nature genetics •
science trans. medicine
mark patterson
managing exec. editor
phil bourne eLife sciences eric schadt
founding editor-in-chief dir. inst. for genomics &
plos comp. biology multiscale biology
mt. sinai school of med.