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detailedLook

Assessing the Significance of Recurrent DNA Copy Number Aberrations


Description

This function applies the "Detailed Look" version of DiNAMIC's cyclic shift procedure to assess the statistical significance of recurrent DNA copy number aberrations. The statistical significance of recurrent gains (gain.loss = "gain") or recurrent losses (gain.loss = "loss") are assessed using an empirical null distribution produced by num.perms cyclic shifts of the DNA copy number matrix x. The null distribution is produced by findNull, which is called internally.

Usage

detailedLook(x, marker.data, annot.file, num.perms, num.iters, 
gain.loss = "gain", reformat.annot = FALSE, random.seed = NULL)

Arguments

x

An n by m numeric matrix containing DNA copy number data from n subjects at m markers.

marker.data

A dataframe containing marker position data for markers in the autosomes. Column 1 contains the chromosome number for each marker, and column 2 contains the position (in base pairs) for each markers. Additional columns, if present, represent information about the markers (e.g. probe names).

annot.file

A cytoband annotation dataframe. Each row corresponds to a distinct cytoband, and column 1 contains the chromosome number, column 2 contains the start position (in base pairs), column 3 contains the end position (in base pairs), and column 4 contains the cytoband name (e.g. p21.3). Additional columns may be present, but they are not used.

num.perms

A positive integer that represents the number of cyclic shifts used to create the empirical null distribution.

num.iters

A positive integer that represents the number of distinct gain (loss) loci that will be assessed. See Details for more information.

gain.loss

A character string that indicates whether recurrent gains (gain.loss = "gain") or recurrent losses (gain.loss = "loss") are assessed.

reformat.annot

A logical value that indicates whether annot.file needs to be reformatted (default = FALSE). See the "note" section of makeCytoband for additional information.

random.seed

An optional random seed (default = NULL).

Details

This function applies the Detailed Look version of DiNAMIC's cyclic shift procedure to assess the statistical significance of recurrent DNA copy number aberrations. Either recurrent gains (gain.loss = "gain") or recurrent losses (gain.loss = "loss") are assessed using a null distribution based on num.perms cyclic shifts of x. Iterative calls to DiNAMIC's peeling procedure (implemented here in the peeling function) allow users to assess the statistical significance of num.iters distinct gains (losses). As noted in Bioinformatics (2011) 27(5) 678 - 685, the Detailed Look procedure recalculates the null distribution after each iteration of the peeling procedure. While this approach is more computationally intensive, simulations suggest that it provides more power to detect recurrent gains (losses).

Value

A matrix with num.iters rows. The entries of each row correspond to the marker that is being assessed. More specifically, the entries are (1) the chromosome number, (2) the marker position (in base pairs), (3) additional marker information present in marker.data, (4) the marker number, and (5) the p-value obtained from the null distribution, (6) the endpoints of the peak interval (in base pairs), as described in Bioinformatics (2011) 27(5) 678 - 685.

Author(s)

Vonn Walter, Andrew B. Nobel, Fred A. Wright

Maintainer: <vwalter@email.unc.edu> Vonn Walter

References

Walter, V., Nobel, A.B., and Wright, F.A., DiNAMIC: a method to identify recurrent DNA copy number aberrations in tumors, Bioinformatics (2011) 27(5) 678 - 685.

Examples

data(wilms.data)
data(wilms.markers)
data(annot.file)
detailedLook(wilms.data, wilms.markers, annot.file, 100, 3)   
#Produces the following output:
#" 1"       "155656176" "R:A-MEXP-192:RP11-393K10" "196"  "0.01"
#"12"       " 38270107" "R:A-MEXP-192:RP11-519E12" "2294" "0.01"
#" 8"       "  4554176" "R:A-MEXP-192:RP11-337D8"  "1659" "0.01"

dinamic

DiNAMIC A Method To Analyze Recurrent DNA Copy Number Aberrations in Tumors

v1.0
GPL-2
Authors
Vonn Walter, Andrew B. Nobel, and Fred A. Wright
Initial release
2011-10-24

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