Inferring causal genomic alterations in breast cancer using gene expression data ( Linh M Tran et.al). By Linglin Huang. A bstract. Background: identify causal genomic alterations in cancer research many valuable studies lack genomic data to detect CNV
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Inferring causal genomic alterations in breast cancer using gene expression data(Linh M Tran et.al)
By Linglin Huang
Preprocessing
data
WACE
algorithm
Gene Regulatory
Network
Inferred CNV
Regions
Key Driver Analysis
Putative Causal
Regulators
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Sample of
Sample of
phenotype
1
phenotype
2
Expression
Score
(
ES
)
of each
gene
:
t

score
Randomly permute
Arrange ES by
Sample labels in
gene physical
calculating ES
location
Neighboring Score
(
NS
)
of each gene
:
Discrete
Wavelet transform
Significant
NS
back
back
back
No parent nodes
Global drivers
d > + σ ( d )
Have parent nodes
Local drivers
d < + σ ( d )
back
back
back
Where is the sample means of the data, is the modified sample variance, is the size of the sample.
back
whereis a given input signal
is a wavelet function at scale a and position s.
The signal can then be reconstructed again from inverse wavelet transform:
where C is a constant.
A scaling level determines the level of decomposition to represent signals at certain resolution. The higher a decomposition level, the lower the resolution of the represented signal.
Each scaling level requires a minimal number of available data, such that s ≤ 1+(N1/)(exp(j)1) where N is number of data and j is the Deubechies filter levels used.
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Such a nonzero mean null distribution increases both type I and type II errors in the statistical evaluation of NS, since for the same magnitude, a negative NS could be assumed to be significant, but the respective positive NS was not.
Randomly assign class labels to each expression values of each gene
VS
Shuffle the
tstatistics( or ES)
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(A)
(B)
GACE
WACE
commonly
commonly
identified loss
identified loss
uniquely
identified loss
uniquely
9%
8%
9%
identified loss
30%
uniquely
36%
45%
identified gain
47%
16%
uniquely
commonly
commonly
identified gain
identified gain
identified gain
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back