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PSB2016 Computational Microbiology Workshop

Casey Greene
Casey Greene

Casey Greene's talk from PSB 2016: http://www.greenelab.com/psb-2016-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-Gy旦rgyi Image by J.W. McGuire/NIH
Image from You Dont 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 Identi鍖es 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 re鍖ects Anr Activity EGEOD17179 }wt } } anr dnr EGEOD17296 } } } } } } anr roxSR anr roxSR wt wt } } EXP STAT O2 EGEOD52445 O2 Node42 - Anr Activity EGEOD33160 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
New Experiment Validates Node 42s Low-O2 Signature CF lung epithelial cells Jack Hammond EGEOD17179 EGEOD17296 B } } anr wt } }anr wt } }an wt 5 0 5 Color Key Value Color Key Value 4 0 4 Color Key Value 2 0 2 Microarray RNAseq PAO1 RNAseq J215 CEGEOD17179 } } anr dnr EGEOD17296 } } }anr roxSR wt }STAT D52445 D33160 B } } anr wt } }anr wt } }anr 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 EGEOD17179 }wt } } anr dnr EGEOD17296 } } } } } } anr roxSR anr roxSR wt wt } } EXP STAT O2 O2 Node42 O2 EGEOD33160 EGEOD52445 PC4 PC7 IC14 }wt } } anr dnr O2 }wt } } anr dnr O2 }wt } } anr dnr O20.5 0 0.51 Value Color Key } } } } } } anr roxSR anr roxSR wt wt } } EXP STAT } } } } } } anr roxSR anr roxSR wt wt } } EXP STAT } } } } } } anr roxSR anr roxSR wt wt } } EXP STAT 1 0 1 2 Value Color Key O2 O2 O221 0 1 2 3 Value Color Key O2 O2 O2 0.5 0.5 1.5 Value Color Key 21 0 1 Value Color Key 321 0 1 Value Color Key 1 0 1 Value Color Key 1 0 1 2 3 4 Value Color Key 1.50.5 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 } } anr dnr O2 } } } } } } anr roxSR anr roxSR 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 } } anr wt Anr-Microarray } } anr wt } } anr wt } } anr wt } } anr 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
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 42s Low-O2 Signature CF lung epithelial cells Jack Hammond EGEOD17179 EGEOD17296 B } } anr wt } }anr wt } }an wt 5 0 5 Color Key Value Color Key Value 4 0 4 Color Key Value 2 0 2 Microarray RNAseq PAO1 RNAseq J215 CEGEOD17179 } } anr dnr EGEOD17296 } } }anr roxSR wt }STAT D52445 D33160 B } } anr wt } }anr wt } }anr 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 EGEOD17179 } } anr dnr EGEOD17296 } } }anr roxSR wt }STAT D52445 D33160 B } } anr wt } }anr wt } }anr 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) Ren辿 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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PSB2016 Computational Microbiology Workshop

  • 1. Research is to see what everybody else has seen and to think what nobody else has thought. Albert Szent-Gy旦rgyi Image by J.W. McGuire/NIH
  • 2. Image from You Dont 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 Identi鍖es 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 re鍖ects Anr Activity EGEOD17179 }wt } } anr dnr EGEOD17296 } } } } } } anr roxSR anr roxSR wt wt } } EXP STAT O2 EGEOD52445 O2 Node42 - Anr Activity EGEOD33160 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 42s Low-O2 Signature CF lung epithelial cells Jack Hammond EGEOD17179 EGEOD17296 B } } anr wt } }anr wt } }an wt 5 0 5 Color Key Value Color Key Value 4 0 4 Color Key Value 2 0 2 Microarray RNAseq PAO1 RNAseq J215 CEGEOD17179 } } anr dnr EGEOD17296 } } }anr roxSR wt }STAT D52445 D33160 B } } anr wt } }anr wt } }anr 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 EGEOD17179 }wt } } anr dnr EGEOD17296 } } } } } } anr roxSR anr roxSR wt wt } } EXP STAT O2 O2 Node42 O2 EGEOD33160 EGEOD52445 PC4 PC7 IC14 }wt } } anr dnr O2 }wt } } anr dnr O2 }wt } } anr dnr O20.5 0 0.51 Value Color Key } } } } } } anr roxSR anr roxSR wt wt } } EXP STAT } } } } } } anr roxSR anr roxSR wt wt } } EXP STAT } } } } } } anr roxSR anr roxSR wt wt } } EXP STAT 1 0 1 2 Value Color Key O2 O2 O221 0 1 2 3 Value Color Key O2 O2 O2 0.5 0.5 1.5 Value Color Key 21 0 1 Value Color Key 321 0 1 Value Color Key 1 0 1 Value Color Key 1 0 1 2 3 4 Value Color Key 1.50.5 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 } } anr dnr O2 } } } } } } anr roxSR anr roxSR 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 } } anr wt Anr-Microarray } } anr wt } } anr wt } } anr wt } } anr 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 42s Low-O2 Signature CF lung epithelial cells Jack Hammond EGEOD17179 EGEOD17296 B } } anr wt } }anr wt } }an wt 5 0 5 Color Key Value Color Key Value 4 0 4 Color Key Value 2 0 2 Microarray RNAseq PAO1 RNAseq J215 CEGEOD17179 } } anr dnr EGEOD17296 } } }anr roxSR wt }STAT D52445 D33160 B } } anr wt } }anr wt } }anr 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 EGEOD17179 } } anr dnr EGEOD17296 } } }anr roxSR wt }STAT D52445 D33160 B } } anr wt } }anr wt } }anr 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) Ren辿 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