The package evaluates DNA copy number data, using both their
initial form (copy number as a noisy function of genomic position) and their
approximation by a piecewise-constant function (segmentation), for the
purpose of identifying genomic regions where the copy number differs from
the norm.
CNpreprocessing(
segall,
ratall = NULL,
idCol = NULL,
startCol = NULL,
endCol = NULL,
medCol = NULL,
madCol = NULL,
errorCol = NULL,
chromCol = NULL,
bpStartCol = NULL,
bpEndCol = NULL,
annot = NULL,
annotStartCol = NULL,
annotEndCol = NULL,
annotChromCol = NULL,
useEnd = FALSE,
blsize = NULL,
minJoin = NULL,
nTrial = 10,
bestBIC = -1e+07,
modelNames = "E",
cWeight = NULL,
bsTimes = NULL,
chromRange = NULL,
nJobs = 1,
normalLength = NULL,
normalMedian = NULL,
normalMad = NULL,
normalError = NULL
)
Arguments
| segall |
a matrix or a data.frame for segmented copy
number profiles. It may have a character column, with a name specified
by idCol, and/or numeric columns with names specified by
startCol, endCol, medCol, madCol,errorCol
,chromCol, bpStartCol, bpEndCol. Each row of segall
corresponds to a segment belonging to one of the profiles
to be pre-processed. |
| ratall |
a matrix whose rows correspond to genomic positions
and columns to copy number profiles. The elements of this matrix are
functions of copy number, most often log ratios of copy number to
the expected standard value, such as 2 in diploid genomes. |
| idCol |
a character string specifying the name for the
column in segall tabulating the profile IDs. When not specified,
the numerical column of the ratall object will be used as the
profile IDs. Default: NULL. |
| startCol |
a character string specifying the name of column
in segall that tabulates the (integer) start position of each segment
in internal units such as probe numbers for data of CGH microarray origin.
Default: NULL. |
| endCol |
a character string specifying the name of column
in segall that tabulates the (integer) end position of each segment
in internal units such as probe numbers for data of CGH microarray origin.
Default: NULL. |
| medCol |
a character string specifying the
name of column in segall that, for the function of copy number used
in the study (typically log ratios), tabulates the (numeric) values for
the function (medCol), a measure of its spread (madCol) and
its error (errorCol) for the segment. Default: NULL. |
| madCol |
a character string specifying the
name of column in segall that, for the function of copy number used
in the study (typically log ratios), tabulates the (numeric) values for
a measure of spread (madCol) related to
the function (medCol) for the segment. Default: NULL. |
| errorCol |
a character string specifying the
name of column in segall that, for the function of copy number used
in the study (typically log ratios), tabulates the (numeric) values for
the error (errorCol) related to
the function (medCol) for the segment. Default: NULL. |
| chromCol |
a character string specifying the name for the
column in segall tabulating the (integer) chromosome number for
each segment. |
| bpStartCol |
a character string specifying the name of
column in segall that tabulates the (integer) genomic start
coordinate of each segment. |
| bpEndCol |
a character string specifying the name of
column in segall that tabulates the (integer) genomic end
coordinate of each segment. |
| annot |
a matrix or a data.frame that contains the
annotation for the copy number measurement platform in the study. It is
generally expected to contain columns with names specified by
annotStartCol, annotEndCol, annotChromCol. |
| annotStartCol |
a character string
specifying the name of column in annot that tabulates the (integer)
genomic start coordinates in case of CGH microarrays. |
| annotEndCol |
a character string
specifying the name of column in annot that tabulates the (integer)
genomic end coordinates in case of CGH microarrays. |
| annotChromCol |
a character string
specifying the name of column in annot that tabulates the chromosome
number for each copy number measuring unit, such as a probe in case of CGH
microarrays. |
| useEnd |
a single logical value specifying whether the segment end
positions as given by the bpEndCol of segall are to be
looked up in the annotEndCol column of annot
(if useEnd=TRUE) or in the annotStartCol column (default).
Default: FALSE. |
| blsize |
a single integer specifying the bootstrap sampling
rate of segment medians to generate input for model-based clustering. The
number of times a segment is sampled is then given by the (integer)
division of the segment length in internal units by blsize. |
| minJoin |
a single numeric value between 0 and 1 specifying the
degree of overlap above which two clusters will be joined into one. Default:
NULL. TODO= HAVE a default value, not NULL. |
| nTrial |
a single positive integer specifying the number of
times a model-based
clustering is attempted for each profile in order to achieve the
highest Bayesian information criterion (BIC). Default: 10. |
| bestBIC |
a single numeric value for initalizing the
Bayesian information criterion (BIC)
maximization. A large negative value is recommended. Default: -1e7. |
| modelNames |
a vector of character strings specifying
the names of models to be used in model-based clustering (see package
mclust for further details). The default is "E". |
| cWeight |
A single numeric value between 0 and 1
specifying the minimal share of the central cluster in each profile. |
| bsTimes |
a single positive double value specifying the number
of time the median of each segment is sampled in order to predict the
cluster assignment for the segment. Default: NULL. TODO: select a
default value that is not null. |
| chromRange |
a integer vector enumerating chromosomes
from which segments are to be used for initial model-based clustering.
Default: NULL. |
| nJobs |
a single positive integer specifying the number of
worker jobs to create in case of distributed computation.
Default: 1 and always 1 for Windows. |
| normalLength |
an integer vector specifying the genomic lengths
of segments in the normal reference data. Default: NULL. |
| normalMedian |
a numeric vector,
of the same length as normalLength, specifying the segment values
of the normal reference segments. Default: NULL. |
| normalMad |
a numeric vector,
of the same length as normalLength, specifying the value spreads
of the normal reference segments. Default: NULL. |
| normalError |
a numeric vector,
of the same length as normalLength, specifying the error values
of the normal reference segments. Default: NULL. |
Value
The input segall data.frame to which some or all of
the following columns may be bound, depending on the availability of input:
segmedian a numeric, the median function of copy number
segmad a numeric, the MAD for the function of copy number
mediandev a numeric, the median function of copy number
relative to its central value
segerr a numeric, the error estimate for the
function of copy number
centerz a numeric between 0 and 1, the
probability that the segment is in the central cluster
marginalprob a numeric, the marginal probability for
the segment in the central cluster
maxz TODO
maxzmean TODO
maxzsigma TODO
samplesize TODO
negtail the probability of finding the deviation as observed or
larger in a collection of central segments
negtailnormad the probability of finding the deviation/MAD as
observed or larger in a collection of central segments
negtailnormerror a numeric, the probability of finding
the deviation/error as observed or larger in a collection of
central segments
Details
Depending on the availability of input, the function will
perform the following operations for each copy number profile.
If raw data are available in addition to segment start and end positions,
median and MAD of each segment will be computed. For each profile, bootstrap
sampling of the segment median values will be performed, and the sample will
be used to estimate the error in the median for each segment.
Model-dependent clustering (fitting to a gaussian mixture) of the sample
will be performed. The central cluster (the one nearest the expected
unaltered value) will be identified and, if necessary, merged with adjacent
clusters in order to comprise the minimal required fraction of the data.
Deviation of each segment from the center, its probability to belong to the
central cluster and its marginal probability in the central cluster will be
computed.
If segment medians or median deviations are available or have been computed,
and, in addition, genomic lengths and average values are given for a
collection of segments with unaltered copy number, additional estimates will
be performed. If median values are available for the unaltered segments, the
marginal probability of the observed median or median deviation in the
unaltered set will be computed for each segment. Likewise, marginal
probabilities for median/MAD and/or median/error will be computed if these
statistics are available.
Author
Alexander Krasnitz
Examples