Integrated Genomic and Proteomic Analyses of aSystematically Perturbed Metabolic Network

Ideker et al. (2001)

Feynman Liang

Amherst College

fliang14@amherst.edu

April 2, 2014

Feynman Liang (AC) Ideker et al. (2001) April 2, 2014 1 / 10

Overview

1 Define an initial model drawn from previous research

2 Systematically perturb each pathway component genetically andenvironmentally

3 Integrate observations with pathway-specific model and globalinteraction network

4 Formulate new hypotheses and design additional pertubations to test

Feynman Liang (AC) Ideker et al. (2001) April 2, 2014 2 / 10

Initial model

Figure 1: Solid lines indicate model of galactose utilization derived from priorresearch

Feynman Liang (AC) Ideker et al. (2001) April 2, 2014 3 / 10

Response of pathway genes

Figure 2: B: Predicted and observed mRNA expression profiles, D: doubling times

Feynman Liang (AC) Ideker et al. (2001) April 2, 2014 4 / 10

Expression profile hierarchical-clustering

Figure 5: Clustering tree constructed using l2-metric of pertubation expressionprofile. Dotted lines indicate additional experiments.

Feynman Liang (AC) Ideker et al. (2001) April 2, 2014 5 / 10

Global mRNA response to pertubations

Figure 2: Gene clusters obtained by training self-organizing map on expressionprofiles

Feynman Liang (AC) Ideker et al. (2001) April 2, 2014 6 / 10

Post-transcription

Figure 3: Protein expression and mRNA change between wt+gal and wt-gal

Feynman Liang (AC) Ideker et al. (2001) April 2, 2014 7 / 10

Integration with global interaction network

Figure 4: Node greyscale intensity: ∆mRNA, yellow: protein→DNA, blue:protein-protein

Feynman Liang (AC) Ideker et al. (2001) April 2, 2014 8 / 10

References

Trey Ideker et al.

Integrated Genomic and Proteomic Analyses of a Systematically PerturbedMetabolic Network

Science 292, 929 (2001)

Feynman Liang (AC) Ideker et al. (2001) April 2, 2014 9 / 10

The End

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