Component: CNGEIntegrator

CNGEIntegrator

Performs one of two possible nonparametric tests for the detection of copy number induced differential gene expression. The tests incorporate the uncertainty of the calling of genomic aberrations: weighted versions of Cramer-von-Mises and Mann-Whitney test statistics are used. An efficient permutation re-sampling procedure is used for p-value calculation. The test statistics may be "shrunken" to borrow information across neighboring genes that share the same copy number signature.

The intCNGEan and CGHcall R packages can be be found here and here.

Version	1.1.0
Bundle	microarray
Categories	Integration Copy Number Analysis
Authors	Riku Louhimo (Riku.Louhimo@Helsinki.FI)
Issue tracker	View/Report issues
Requires	intCNGEan (R-package) ; impute (R-bioconductor) ; CGHcall (R-bioconductor) ; DNAcopy (R-bioconductor)
Source files	component.xml CNGEIntegrator.r
Usage	Example with default values CNGEIntegrator( CNAProbLoss = CSV, CNAProbGain = CSV, CNAProbNorm = CSV, exprMatrix = CSV, exprAnnotation = AnnotationTable, FDRLimit = 0.05, analysisType = "univariate", matchMethod = "overlap", nGenesTune = 50, nperm = <int>, testStatistic = "wmw" )

Version

1.1.0

Bundle

microarray

Categories

Integration Copy Number Analysis

Authors

Riku Louhimo (Riku.Louhimo@Helsinki.FI)

Issue tracker

View/Report issues

Requires

intCNGEan (R-package) ; impute (R-bioconductor) ; CGHcall (R-bioconductor) ; DNAcopy (R-bioconductor)

Source files

component.xml CNGEIntegrator.r

Usage

Example with default values

Inputs

Name	Type	Mandatory	Description
CNAProbLoss	CSV	Mandatory	Matrix of probabilities for probewise copy number losses as output by ACGHsegment component.
CNAProbGain	CSV	Mandatory	Matrix of probabilities for probewise copy number gains as output by ACGHsegment component.
CNAProbNorm	CSV	Mandatory	Matrix of probabilities for probewise copy number alterations as output by ACGHsegment component.
exprMatrix	CSV	Mandatory	Expression matrix.
exprAnnotation	AnnotationTable	Mandatory	Probe annotations for the expression matrix. Must contain columns 'Chr' and 'Start'.

Name

Type

Mandatory

Description

CNAProbLoss

CSV

Mandatory

Matrix of probabilities for probewise copy number losses as output by ACGHsegment component.

CNAProbGain

CSV

Mandatory

Matrix of probabilities for probewise copy number gains as output by ACGHsegment component.

CNAProbNorm

CSV

Mandatory

Matrix of probabilities for probewise copy number alterations as output by ACGHsegment component.

exprMatrix

CSV

Mandatory

Expression matrix.

exprAnnotation

AnnotationTable

Mandatory

Probe annotations for the expression matrix. Must contain columns 'Chr' and 'Start'.

Outputs

Name	Type	Description
integrationResult	CSV	Results of the integration. If analysisType="univariate", the component returns a CSV with the following columns: the first three columns contain the annotation information; the gene number of the original (pre-tuned, matched) data set; indicator of test performed, either "1" (loss vs. no-loss) or "2" (no-gain vs. gain); the estimated marginal call probability distribution (two columns); the estimated copy number induced gene expression change; the coefficient of determination; the raw p-value; the BH-corrected p-value. If analysis.type="regional", the component returns a CSV with the following columns: the first three columns contain the annotation information; the gene number of the original (pre-tuned, matched) data set; indicator of test performed, either "1" (loss vs. no-loss) or "2" (no-gain vs. gain); the estimated marginal call probability distribution (two columns); the estimated copy number induced gene expression change; the coefficient of determination; the region number within chromosome; gene number of first and last gene within the region (two columns); shrinkage parameter; the raw p-value; the BH-corrected p-value.

Name

Type

Description

integrationResult

CSV

Results of the integration. If analysisType="univariate", the component returns a CSV with the following columns: the first three columns contain the annotation information; the gene number of the original (pre-tuned, matched) data set; indicator of test performed, either "1" (loss vs. no-loss) or "2" (no-gain vs. gain); the estimated marginal call probability distribution (two columns); the estimated copy number induced gene expression change; the coefficient of determination; the raw p-value; the BH-corrected p-value. If analysis.type="regional", the component returns a CSV with the following columns: the first three columns contain the annotation information; the gene number of the original (pre-tuned, matched) data set; indicator of test performed, either "1" (loss vs. no-loss) or "2" (no-gain vs. gain); the estimated marginal call probability distribution (two columns); the estimated copy number induced gene expression change; the coefficient of determination; the region number within chromosome; gene number of first and last gene within the region (two columns); shrinkage parameter; the raw p-value; the BH-corrected p-value.

Parameters

Name	Type	Default	Description
FDRLimit	float	0.05	False-discover rate corrected p-value threshold.
analysisType	string	"univariate"	Determine whether to shrink test statistic or not. Defaults to non-shrinkage.
matchMethod	string	"overlap"	Matching occurs on the basis of genomic locations. In case matchMethod="distance", the midpoint of copy number and expression probes are calculated and for each gene on the expression array the closest feature of the copy number platform is selected. If matchMethod="overlap", each gene in the expression array is matched to the feature from the copy number platform with the maximum percentage of overlap. If the maximum percentage of overlap equals zero, the gene is not included in the matched objects. If matchMethod="overlapplus", the features are first matched by their percentage of overlap (as with the matchMethod="overlap"-option). For all non-matched expression probes, the closest two copy number features (one down- and one upstream) are determined. If the copy number signature of these two copy number probes is identical, intrapolation seems reasonable, and the expression probe is matched to the closest of these two CN probes. Hence, matchMethod="overlapplus" makes use of the copy number data, consequently, matching may be different for different data sets.
nGenesTune	int	50	Number of genes used in the tuning step.
nperm	int	(no default)	Number of permutations in the integration permutation test.
testStatistic	string	"wmw"	Test statistic to be used. Either "wcvm" for weighted Cramer-von-Mises statistic or "wmw" for weighted Mann-Whitney test statistic.

Name

Type

Default

Description

FDRLimit

float

0.05

False-discover rate corrected p-value threshold.

analysisType

string

"univariate"

Determine whether to shrink test statistic or not. Defaults to non-shrinkage.

matchMethod

string

"overlap"

Matching occurs on the basis of genomic locations. In case matchMethod="distance", the midpoint of copy number and expression probes are calculated and for each gene on the expression array the closest feature of the copy number platform is selected. If matchMethod="overlap", each gene in the expression array is matched to the feature from the copy number platform with the maximum percentage of overlap. If the maximum percentage of overlap equals zero, the gene is not included in the matched objects. If matchMethod="overlapplus", the features are first matched by their percentage of overlap (as with the matchMethod="overlap"-option). For all non-matched expression probes, the closest two copy number features (one down- and one upstream) are determined. If the copy number signature of these two copy number probes is identical, intrapolation seems reasonable, and the expression probe is matched to the closest of these two CN probes. Hence, matchMethod="overlapplus" makes use of the copy number data, consequently, matching may be different for different data sets.

nGenesTune

int

Number of genes used in the tuning step.

nperm

int

(no default)

Number of permutations in the integration permutation test.

testStatistic

string

"wmw"

Test statistic to be used. Either "wcvm" for weighted Cramer-von-Mises statistic or "wmw" for weighted Mann-Whitney test statistic.

Test cases

Test case	Parameters▼	IN CNAProbLoss	IN CNAProbGain	IN CNAProbNorm	IN exprMatrix	IN exprAnnotation	OUT integrationResult
case1	properties	CNAProbLoss	CNAProbGain	CNAProbNorm	exprMatrix	exprAnnotation	integrationResult
	FDRLimit=0.5, analysisType=regional, nperm=10
case2	properties	CNAProbLoss	CNAProbGain	CNAProbNorm	exprMatrix	exprAnnotation	integrationResult
	matchMethod=distance, nperm=10

Test case

Parameters▼

IN
CNAProbLoss

IN
CNAProbGain

IN
CNAProbNorm

IN
exprMatrix

IN
exprAnnotation

OUT
integrationResult

case1

properties

CNAProbLoss

CNAProbGain