Casey Greene's talk from PSB 2016: http://www.greenelab.com/psb-2016-computational-microbiology-workshop/

1. Research is to see what everybody
else has seen and to think what
nobody else has thought.
Albert Szent-Györgyi
Image by J.W. McGuire/NIH

2. Image from You Don’t Know Jack. Vol 3.

3. Unsupervised discovery
from large gene expression
compendia with ADAGE
Casey Greene

4. Analysis with Denoising Autoencoders of
Gene Expression (ADAGE)
Tan et al. Pac Sym Bio 2015; Tan et al. In Press. mSystems

5. ADAGE Identifies Genes’ Pathways
Assign
Pathway

6. … and produces useful networks

7. The Transcription Factor Anr
Controls P.a. Response to Low O2
Low O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
Anr
CF Lung Epithelium

8. Node42 reflects Anr Activity
E−GEOD−17179
}wt
}
}
Δanr
Δdnr
E−GEOD−17296
}
}
}
}
}
}
Δanr
ΔroxSR
Δanr
ΔroxSR
wt
wt
}
}
EXP
STAT
O2
E−GEOD−52445
O2
Node42 - Anr Activity
E−GEOD−33160
O2
A
−15 0 10
Value
Color Key Color Key
−10 0 10
Value
Color Key
Value
−10 0 10
−10 0 15
Color Key
Value

9. New Experiment Validates Node 42’s
Low-O2 Signature
CF lung epithelial cells
Jack Hammond
E−GEOD−17179 E−GEOD−17296
B
}
}
Δanr
wt
}
}Δanr
wt }
}Δan
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
}
}
Δanr
Δdnr
E−GEOD−17296
}
}
}Δanr
ΔroxSR
wt
}STAT
D−52445
D−33160
B
}
}
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

10. ADAGE complements PCA/ICA
E−GEOD−17179
}wt
}
}
Δanr
Δdnr
E−GEOD−17296
}
}
}
}
}
}
Δanr
ΔroxSR
Δanr
ΔroxSR
wt
wt
}
}
EXP
STAT
O2
O2
Node42
O2
E−GEOD−33160
E−GEOD−52445
PC4 PC7 IC14
}wt
}
}
Δanr
Δdnr
O2
}wt
}
}
Δanr
Δdnr
O2
}wt
}
}
Δanr
Δdnr
O2−0.5 0 0.51
Value
Color Key
}
}
}
}
}
}
Δanr
ΔroxSR
Δanr
ΔroxSR
wt
wt
}
}
EXP
STAT
}
}
}
}
}
}
Δanr
ΔroxSR
Δanr
ΔroxSR
wt
wt
}
}
EXP
STAT
}
}
}
}
}
}
Δanr
ΔroxSR
Δanr
ΔroxSR
wt
wt
}
}
EXP
STAT
−1 0 1 2
Value
Color Key
O2 O2 O2−2−1 0 1 2 3
Value
Color Key
O2 O2 O2
−0.5 0.5 1.5
Value
Color Key
−2−1 0 1
Value
Color Key
−3−2−1 0 1
Value
Color Key
−1 0 1
Value
Color Key
−1 0 1 2 3 4
Value
Color Key
−1.5−0.5 0.5
Value
Color Key
−0.5 0 0.5
Value
Color Key
−0.4 0 0.4
Value
Color Key
−1 0 1 2
Value
Color Key
IC49
}wt
}
}
Δanr
Δdnr
O2
}
}
}
}
}
}
Δanr
ΔroxSR
Δanr
ΔroxSR
wt
wt
}
}
EXP
STAT
O2
O2
Color Key
Color Key
Color Key
−1 0 1
Value
Color Key
−0.5 0.5 1.5
Value
−0.5 0 0.51
Value
−1 0 1 2
Value
}
}
Δanr
wt
Anr-Microarray
}
}
Δanr
wt
}
}
Δanr
wt
}
}
Δanr
wt
}
}
Δanr
wt
Value
Color Key
Value
Color Key
Value
Color Key
Value
Color Key
−0.6 0.60 −0.1 0 0.1 −0.1 0 0.1 0.2 −0.1 0 0.1
−15 0 10
Value
Color Key
Color Key
−10 0 10
Value
Color Key
Value
−10 0 10
−10 0 15
Color Key
Value
−5 0 5
Color Key
Value

11. Cross-platform normalization of microarray and
RNA-seq data for machine learning applications
Thompson, Tan, Greene. In Press. PeerJ. https://peerj.com/preprints/1460/
Jeff Thompson

12. Cross-platform normalization of microarray and
RNA-seq data for machine learning applications
Thompson, Tan, Greene. In Press. PeerJ. https://peerj.com/preprints/1460/

13. New Experiment Validates Node 42’s
Low-O2 Signature
CF lung epithelial cells
Jack Hammond
E−GEOD−17179 E−GEOD−17296
B
}
}
Δanr
wt
}
}Δanr
wt }
}Δan
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
}
}
Δanr
Δdnr
E−GEOD−17296
}
}
}Δanr
ΔroxSR
wt
}STAT
D−52445
D−33160
B
}
}
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
}
}
Δanr
Δdnr
E−GEOD−17296
}
}
}Δanr
ΔroxSR
wt
}STAT
D−52445
D−33160
B
}
}
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

14. ADAGE analysis of publicly available
gene expression data collections
illuminates Pseudomonas aeruginosa-
host interactions
bioRxiv: http://dx.doi.org/10.1101/030650
In Press @ mSystems

15. How do we move from
this to mechanisms?
What “pathways” did my
experiment affect?

16. ADAGE-based Pathway Analysis
of Transcriptomic Changes

17. ADAGE Webserver coming soon!
http://www.greenelab.com/webservers

18. Jie Tan+ (Grad Student)
Gregory Way (Grad Student)
Brett Beaulieu-Jones (Grad Student)
René Zelaya (Programmer)
Matt Huyck (Programmer)
Kathy Chen (Undergrad)
Mulin Xiong (Undergrad)
Deb Hogan (Hogan Lab/Dartmouth)
Jack Hammond (Hogan Lab/Dartmouth)
Jeff Thompson (Marsit Lab/Dartmouth)
Data:
All investigators who publicly release their
gene expression data.
Images:
Artists who release their work under a
Creative Commons license.
Funding:
G&B Moore Investigator in Data-Driven Discovery
National Science Foundation
Cystic Fibrosis Foundation
Norris Cotton Cancer Center Prouty Grant
American Cancer Society
Dartmouth SYNERGY
+Neukom Institute Graduate Fellowship
Find us online:
http://www.greenelab.com
Twitter: @GreeneScientist