Visual analysis of genome-scale datasets

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Visual analysis of genome-scale datasets

Visual analysis of genome-scale datasets
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Classical tree view of cell cycle data
(Spellman, et al. 1998. MolBiolCell 9, 3273)
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VxInsight topography of cell-cycle data
G1
S
M
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Strong similarities show relationships among
clusters
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How can we learn more from this analysis?
Genome-scale datasets available in yeast

• Essential genes

• Essential genes since 1998

• Several microarray datasets

• Protein-protein interactions

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Essential genes as a function of gene expression
what does it tell us?
Ribosome ridge
Stationary-phase genes are not essential
Essential genes
Newly identified essential genes
Assumptions biases potentially new, useful
targets, how cells protect themselves
evolution, etc.
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Comparison of gene-expression datasets to test
hypotheses
Are G1-regulated genes clustered during exit from
stationary phase?
Cell cycle
Exit from stationary phase
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What might this say? Exit from stationary phase
is either 1) not a synchronous process with
respect to the cell cycle. 2) a cell-cycle
process that requires a subset of cell-cycle
genes
Exit from stationary phase

• If this is true, the two processes may be
• sensitive to different toxins.
• This has important implications in
• treatment of infectious diseases
• if the infectious agent spends a great deal
• of time in the quiescent state
• This may also help us understand why
• unculturable microorganisms cant exit
• stationary phase

Cell cycle
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Protein -interaction networks as a function of
gene expression
Ito full dataset
Schwikowskis data
Conclusions 1. Interactions do not generally
follow expression patterns 2. Few interactions
common to both datasets 3. Need to look at
specific clusters, known interactions to
determine whether one dataset should be accepted
or whether the data should be combined
Genes common to both
Interactions common to both
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A
Exit from stationary phase Ribosome ridge. 290
genes
B
Similarity in gene expression
Conclusion Two-hybrid methods dont see
interactions between ribosomal proteins
In fact, there may not be many interactions among
ribosomal proteins so this may be the strongest
evidence for the lack of false positives in this
analysis
C
Interactions in ribosome ridge
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Summary Visualization of the datasets enables a
more intuitive approach and speeds hypothesis
development
Visual comparison of genome-scale datasets
supports
Faster and broader evaluation of the datasets
Identification of biases and assumptions in our
methods
Novel insights into biological processes ? new
and more focused questions
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The Biological Process the yeast cell cycle
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VxInsight clustering of exit from stationary
phase data T0, 15, 30, 45, and 60 minutes after
re-feeding