Gone Fishing (From the PSB No Boundary Thinking Workshop)
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Transcript of Gone Fishing (From the PSB No Boundary Thinking Workshop)
Image by anujraj (flickr)
Casey Greene
The worst thing that can be said about your grant is that it's a fishing expedition.
�- Tom Blumenthal (@ 2016 Gold Lab Symposium)
• Pseudomonas aeruginosa compendium • > 100 different experiments • Many different labs • ~$1 million in direct costs
Image from You Don’t Know Jack. Vol 3.
Analysis with Denoising Autoencoders of �Gene Expression (ADAGE)
Tan et al. Pac Sym Bio 2015; Tan et al. mSystems 2016.
Node42 reflects Anr Activity
E−GEOD−17179
} wt
}}Δanr
Δdnr
E−GEOD−17296
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
wt
wt
}}
EXP
STAT
O2
E−GEO
D−52445
O2
Node42 - Anr ActivityE−G
EOD
−33160
O2
A
B
−15 0 10Value
Color KeyColor Key
−10 0 10Value
Color Key
Value−10 0 10
−10 0 15
Color Key
Value
}}Δanr
wt
}}Δanr
wt }}Δanr
wt
−5 0 5
Color Key
Value
Color Key
Value−4 0 4
Color Key
Value−2 0 2
Microarray RNAseq PAO1
RNAseq J215
C
New Experiment Validates Node 42’s Low-O2 Signature
CF lung epithelial cells Jack Hammond
E−GEOD−17179
} wt
}}Δanr
Δdnr
E−GEOD−17296
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
wt
wt
}}
EXP
STAT
O2
E−GEO
D−52445
O2
Node42 - Anr Activity
E−GEO
D−33160
O2
A
B
−15 0 10Value
Color KeyColor Key
−10 0 10Value
Color Key
Value−10 0 10
−10 0 15
Color Key
Value
}}Δanr
wt
}}Δanr
wt }}Δanr
wt
−5 0 5
Color Key
Value
Color Key
Value−4 0 4
Color Key
Value−2 0 2
Microarray RNAseq PAO1
RNAseq J215
CE−GEOD−17179
} wt
}}Δanr
Δdnr
E−GEOD−17296
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
wt
wt
}}
EXP
STAT
O2
E−GEO
D−52445
O2
Node42 - Anr Activity
E−GEO
D−33160
O2
A
B
−15 0 10Value
Color KeyColor Key
−10 0 10Value
Color Key
Value−10 0 10
−10 0 15
Color Key
Value
}}Δanr
wt
}}Δanr
wt }}Δanr
wt
−5 0 5
Color Key
Value
Color Key
Value−4 0 4
Color Key
Value−2 0 2
Microarray RNAseq PAO1
RNAseq J215
C
E−GEOD−17179
} wt
}}Δanr
Δdnr
E−GEOD−17296
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
wt
wt
}}
EXP
STAT
O2
E−GEO
D−52445
O2
Node42 - Anr Activity
E−GEO
D−33160
O2
A
B
−15 0 10Value
Color KeyColor Key
−10 0 10Value
Color Key
Value−10 0 10
−10 0 15
Color Key
Value
}}Δanr
wt
}}Δanr
wt }}Δanr
wt
−5 0 5
Color Key
Value
Color Key
Value−4 0 4
Color Key
Value−2 0 2
Microarray RNAseq PAO1
RNAseq J215
C
E−GEOD−17179
} wt
}}Δanr
Δdnr
E−GEOD−17296
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
wt
wt
}}
EXP
STAT
O2
E−GEO
D−52445
O2
Node42 - Anr Activity
E−GEO
D−33160
O2
A
B
−15 0 10Value
Color KeyColor Key
−10 0 10Value
Color Key
Value−10 0 10
−10 0 15
Color Key
Value
}}Δanr
wt
}}Δanr
wt }}Δanr
wt
−5 0 5
Color Key
Value
Color Key
Value−4 0 4
Color Key
Value−2 0 2
Microarray RNAseq PAO1
RNAseq J215
C
E−GEOD−17179
} wt
}}Δanr
Δdnr
E−GEOD−17296
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
wt
wt
}}
EXP
STAT
O2
E−GEO
D−52445
O2
Node42 - Anr Activity
E−GEO
D−33160
O2
A
B
−15 0 10Value
Color KeyColor Key
−10 0 10Value
Color Key
Value−10 0 10
−10 0 15
Color Key
Value
}}Δanr
wt
}}Δanr
wt }}Δanr
wt
−5 0 5
Color Key
Value
Color Key
Value−4 0 4
Color Key
Value−2 0 2
Microarray RNAseq PAO1
RNAseq J215
C
Image: Al Stephenson. EPA National Archives
Image: Jan Derk
Does combining consistent patterns across neural networks
clarify biological signatures?
eADAGE node 164 captures phosphate concentration in
media.
Georgia Doing and Jie Tan
Low Phosphate
PhoB (TF)
Alkaline phosphatase
BCIP Blue color
PhoR
The phosphate starvation pathway… is incomplete.
The phosphate starvation pathway… is incomplete.
Low Phosphate
PhoB (TF)
Alkaline phosphatase
BCIP Blue color
PhoR ?
Public data suggests the alternative mechanism.
GSE48429 – PIA vs. PIA + ammonium metavanadate (July 2013)
GSE35248 – ΔKinB vs ΔKinB/ΔRpoN (March 2012)
kinB is necessary for activity on intermediate phosphate levels.
Unsupervised extraction of functional gene expression signatures in the bacterial pathogen Pseudomonas aeruginosa with eADAGE��bioRxiv: http://dx.doi.org/10.1101/078659�bitbucket: http://bitbucket.org/greenelab/eadage�Tan*, Doing*, et al.
2,198,423 assays ~$2.2 billion
The worst thing that can be said about your grant is that it's a fishing expedition.
�- Tom Blumenthal (@ 2016 Gold Lab Symposium)
�- Tom Blumenthal (@ 2016 Gold Lab Symposium)
If you engage in a fishing expedition you can actually catch fish.�
Image by Peter (stockispicts)
Greene Lab: Jaclyn Taroni (Postdoc) Daniel Himmelstein (Postdoc) Jie Tan (Grad Student) Gregory Way (Grad Student) Brett Beaulieu-Jones (Grad Student) Amy Campbell (Postbacc) René Zelaya (Programmer) Matt Huyck (Programmer) Dongbo Hu (Programmer) Kathy Chen (Undergrad) Tim Chang (Undergrad) Roshan Ravishankar (Undergrad)
Collaborators: Deb Hogan, Georgia Doing, Kimberley Lewis & Jack Hammond
Data: All investigators who publicly release their gene expression data.
Images: Artists who release their work under a Creative Commons license.
Funding: Gordon and Betty Moore Foundation National Science Foundation Cystic Fibrosis Foundation National Institutes of Health �
Find us online: http://www.greenelab.com
Calvin and Hobbes. Bill Watterson
