psb2016 computational microbiology workshop
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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
Image from You Don’t Know Jack. Vol 3.
Unsupervised discovery �from large gene expression compendia with ADAGE
Casey Greene
Analysis with Denoising Autoencoders of �Gene Expression (ADAGE)
Tan et al. Pac Sym Bio 2015; Tan et al. In Press. mSystems
ADAGE Identifies Genes’ Pathways
Assign Pathway
… and produces useful networks
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
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
ADAGE complements PCA/ICA
E−GEOD−17179} wt
}}Δanr
Δdnr
E−GEOD−17296
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
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 0.51Value
Color Key
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
wt
wt
}}
EXP
STAT
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
wt
wt
}}
EXP
STAT
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
wt
wt
}}
EXP
STAT
−1 0 1 2Value
Color Key
O2 O2 O2−2−1 0 1 2 3Value
Color Key
O2 O2 O2−0.5 0.5 1.5
Value
Color Key
−2−1 0 1Value
Color Key
−3−2−1 0 1Value
Color Key
−1 0 1Value
Color Key
−1 0 1 2 3 4Value
Color Key
−1.5−0.5 0.5Value
Color Key
−0.5 0 0.5Value
Color Key
−0.4 0 0.4Value
Color Key
−1 0 1 2Value
Color Key
IC49
} wt
}}Δanr
Δdnr
O2
}}}}}}
ΔanrΔroxSR
ΔanrΔroxSR
wt
wt
}}
EXP
STAT
O2
O2
Color Key
Color Key
Color Key
−1 0 1Value
Color Key
−0.5 0.5 1.5Value
−0.5 0 0.51Value
−1 0 1 2Value
}}Δanr
wt
}Δanr
wt
Anr-Microarray
Anr-RNAseq
}}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
Value
Color Key
Value
Color Key
Value
Color Key
Value
Color Key
−15 0 10Value
Color Key
Color Key
−10 0 10Value
Color Key
Value−10 0 10
−10 0 15
Color Key
Value
−5 0 5
Color Key
Value
Color Key
Value
}}}
}}
Δanr
wt
PAO1
J215
}Δanr
wt
}}}
}}
Δanr
wt
PAO1
J215
}Δanr
wt
}}}
}}
Δanr
wt
PAO1
J215
}Δanr
wt
}}}
}}
Δanr
wt
PAO1
J215
}Δanr
wt
}}}
}}
Δanr
wt
PAO1
J215
−10 0 10 −1.5 0 1 −1 0 1 −0.05 0 0.1 −0.2 0 0.2
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
Cross-platform normalization of microarray and RNA-seq data for machine learning applications
Thompson, Tan, Greene. In Press. PeerJ. https://peerj.com/preprints/1460/
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
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
How do we move from �this to mechanisms?
What “pathways” did my experiment affect?
ADAGE-based Pathway Analysis of Transcriptomic Changes
ADAGE Webserver coming soon! http://www.greenelab.com/webservers
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
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