DNAcopy (version 1.46.0)

segment: Genome Segmentation Program

Description

This program segments DNA copy number data into regions of estimated equal copy number using circular binary segmentation (CBS).

Usage

segment(x, weights = NULL, alpha = 0.01, nperm = 10000, p.method =  c("hybrid", "perm"), min.width=2, kmax=25, nmin=200,  eta=0.05, sbdry=NULL, trim = 0.025, undo.splits =  c("none", "prune", "sdundo"), undo.prune=0.05,  undo.SD=3, verbose=1)

Arguments

x

an object of class CNA

weights

a vector of weights for the probes. The weights should be inversely proportional to their variances. Currently all weights should be positive i.e. remove probes with zero weight prior to segmentation.

alpha

significance levels for the test to accept change-points.

nperm

number of permutations used for p-value computation.

p.method

method used for p-value computation. For the "perm" method the p-value is based on full permutation. For the "hybrid" method the maximum over the entire region is split into maximum of max over small segments and max over the rest. Approximation is used for the larger segment max. Default is hybrid.

min.width

the minimum number of markers for a changed segment. The default is 2 but can be made larger. Maximum possible value is set at 5 since arbitrary widths can have the undesirable effect of incorrect change-points when a true signal of narrow widths exists.

kmax

the maximum width of smaller segment for permutation in the hybrid method.

nmin

the minimum length of data for which the approximation of maximum statistic is used under the hybrid method. should be larger than 4*kmax

eta

the probability to declare a change conditioned on the permuted statistic exceeding the observed statistic exactly j (= 1,...,nperm*alpha) times.

sbdry

the sequential boundary used to stop and declare a change. This boundary is a function of nperm, alpha and eta. It can be obtained using the function "getbdry" and used instead of having the "segment" function compute it every time it is called.

trim

proportion of data to be trimmed for variance calculation for smoothing outliers and undoing splits based on SD.

undo.splits

A character string specifying how change-points are to be undone, if at all. Default is "none". Other choices are "prune", which uses a sum of squares criterion, and "sdundo", which undoes splits that are not at least this many SDs apart.

undo.prune

the proportional increase in sum of squares allowed when eliminating splits if undo.splits="prune".

undo.SD

the number of SDs between means to keep a split if undo.splits="sdundo".

verbose

level of verbosity for monitoring the program's progress where 0 produces no printout, 1 prints the current sample, 2 the current chromosome and 3 the current segment. The default level is 1.

Value

An object of class DNAcopy. It has three elements:

data

The original CNA object which was the input for segment

out

a data frame with six columns. Each row of the data frame contains a segment for which there are six variables: the sample id, the chromosome number, the map position of the start of the segment, the map position of the end of the segment, the number of markers in the segment, and the average value in the segment.

segRows

a data frame with the start and end row of each segment in the data matrix. print command shows it with the showSegRows=T

call

the call that produced the output object.

Details

This function implements the cicular binary segmentation (CBS) algorithm of Olshen and Venkatraman (2004). Given a set of genomic data, either continuous or binary, the algorithm recursively splits chromosomes into either two or three subsegments based on a maximum t-statistic. A reference distribution, used to decided whether or not to split, is estimated by permutation. Options are given to eliminate splits when the means of adjacent segments are not sufficiently far apart. Note that after the first split the $\alpha$-levels of the tests for splitting are not unconditional.

We recommend using one of the undoing options to remove change-points detected due to local trends (see the manuscript below for examples of local trends).

Since the segmentation procedure uses a permutation reference distribution, R commands for setting and saving seeds should be used if the user wishes to reproduce the results.

Data that are NA, Inf, NaN will be removed on a per sample basis for "genomdat" and all samples for "chrom" and "maploc".

References

Olshen, A. B., Venkatraman, E. S., Lucito, R., Wigler, M. (2004). Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics 5: 557-572.

Venkatraman, E. S., Olshen, A. B. (2007) A faster circular binary segmentation algorithm for the analysis of array CGH data. Bioinformatics 23: 657-63.

Examples

# test code on an easy data set
set.seed(25)
genomdat <- rnorm(500, sd=0.1) +
rep(c(-0.2,0.1,1,-0.5,0.2,-0.5,0.1,-0.2),c(137,87,17,49,29,52,87,42))
plot(genomdat)
chrom <- rep(1:2,c(290,210))
maploc <- c(1:290,1:210)
test1 <- segment(CNA(genomdat, chrom, maploc))

# test code on a noisier and hence more difficult data set
set.seed(51)
genomdat <- rnorm(500, sd=0.2) +
rep(c(-0.2,0.1,1,-0.5,0.2,-0.5,0.1,-0.2),c(137,87,17,49,29,52,87,42))
plot(genomdat)
chrom <- rep(1:2,c(290,210))
maploc <- c(1:290,1:210)
test2 <- segment(CNA(genomdat, chrom, maploc))

# test code for weighted CBS
set.seed(97)
wts <- sample(1:3, 500, replace=TRUE)
genomdat <- rnorm(500, sd=0.3)/sqrt(wts) +
rep(c(-0.2,0.1,1,-0.5,0.2,-0.5,0.1,-0.2),c(137,87,17,49,29,52,87,42))
plot(genomdat)
chrom <- rep(1:2,c(290,210))
maploc <- c(1:290,1:210)
test3 <- segment(CNA(genomdat, chrom, maploc), weights=wts)

#A real analyis

data(coriell)

#Combine into one CNA object to prepare for analysis on Chromosomes 1-23

CNA.object <- CNA(cbind(coriell$Coriell.05296,coriell$Coriell.13330),
                  coriell$Chromosome,coriell$Position,
                  data.type="logratio",sampleid=c("c05296","c13330"))

#We generally recommend smoothing single point outliers before analysis
#Make sure to check that the smoothing is proper

smoothed.CNA.object <- smooth.CNA(CNA.object)

#Segmentation at default parameters

segment.smoothed.CNA.object <- segment(smoothed.CNA.object, verbose=1)
data(coriell)

#Combine into one CNA object to prepare for analysis on Chromosomes 1-23

CNA.object <- CNA(cbind(coriell$Coriell.05296,coriell$Coriell.13330),
                  coriell$Chromosome,coriell$Position,
                  data.type="logratio",sampleid=c("c05296","c13330"))

#We generally recommend smoothing single point outliers before analysis
#Make sure to check that the smoothing is proper

smoothed.CNA.object <- smooth.CNA(CNA.object)

#Segmentation at default parameters

segment.smoothed.CNA.object <- segment(smoothed.CNA.object, verbose=1)