Package 'VanillaICE'

Title: A Hidden Markov Model for high throughput genotyping arrays
Description: Hidden Markov Models for characterizing chromosomal alteration in high throughput SNP arrays.
Authors: Robert Scharpf [aut, cre]
Maintainer: Robert Scharpf <[email protected]>
License: LGPL-2
Version: 1.67.0
Built: 2024-06-30 05:59:53 UTC
Source: https://github.com/bioc/VanillaICE

Help Index


Calculate lag10 autocorrelation

Description

A wrapper for the function acf that returns the autocorrelation for the specified lag. Missing values are removed.

Usage

acf2(x, lag = 10, ...)

Arguments

x

numeric vector

lag

integer

...

additional arguments to acf

See Also

acf


ArrayViews class, constructor, and methods

Description

ArrayViews provides views to the low-level data – log R ratios, B allele frequencies, and genotypes that are stored in parsed files on disk, often scaled and coerced to an integer. Accessors to the low-level data are provided that extract the marker-level summaries from disk, rescaling when appropriate.

Usage

ArrayViews(
  class = "ArrayViews",
  colData,
  rowRanges = GRanges(),
  sourcePaths = character(),
  scale = 1000,
  sample_ids,
  parsedPath = getwd(),
  lrrFiles = character(),
  bafFiles = character(),
  gtFiles = character()
)

## S4 method for signature 'ArrayViews,ANY,ANY,ANY'
x[i, j, ..., drop = FALSE]

colnames(x) <- value

## S4 method for signature 'ArrayViews'
colnames(x, do.NULL = TRUE, prefix = "col")

## S4 method for signature 'ArrayViews'
x$name

## S4 replacement method for signature 'ArrayViews'
x$name <- value

## S4 method for signature 'ArrayViews'
show(object)

## S4 method for signature 'ArrayViews'
sapply(X, FUN, ..., simplify = TRUE, USE.NAMES = TRUE)

## S4 method for signature 'ArrayViews'
ncol(x)

## S4 method for signature 'ArrayViews'
nrow(x)

## S4 method for signature 'ArrayViews'
dim(x)

## S4 method for signature 'ArrayViews'
start(x)

Arguments

class

character string

colData

DataFrame

rowRanges

GRanges object

sourcePaths

character string provide complete path to plain text source files (one file per sample) containing log R ratios and B allele frequencies

scale

log R ratios and B allele frequencies can be stored as integers on disk to increase IO speed. If scale =1, the raw data is not transformed. If scale = 1000 (default), the log R ratios and BAFs are multipled by 1000 and coerced to an integer.

sample_ids

character vector indicating how to name samples. Ignored if colData is specified.

parsedPath

character vector indicating where parsed files should be saved

lrrFiles

character vector of file names for storing log R ratios

bafFiles

character vector of file names for storing BAFs

gtFiles

character vector of file names for storing genotypes

x

a ArrayViews object

i

numeric vector or missing

j

numeric vector or missing

...

additional arguments to FUN

drop

ignored

value

a character-string vector

do.NULL

ignored

prefix

ignored

name

character string indicating name in colData slot of ArrayViews object

object

a ArrayViews object

X

a ArrayViews object

FUN

a function to apply to each column of X

simplify

logical indicating whether result should be simplied

USE.NAMES

whether the output should be a named vector

Slots

colData

A character string

rowRanges

A DataFrame. WARNING: The accessor for this slot is rowRanges, not rowRanges!

index

A GRanges object

sourcePaths

A character string providing complete path to source files (one file per sample) containing low-level summaries (Log R ratios, B allele frequencies, genotypes)

scale

A length-one numeric vector

parsedPath

A character string providing full path to where parsed files should be saved

lrrFiles

character vector of filenames for log R ratios

bafFiles

character vector of filenames for BAFs

gtFiles

character vector of filenames for genotypes

See Also

CopyNumScanParams parseSourceFile

Examples

ArrayViews()
## From unit test
  require(BSgenome.Hsapiens.UCSC.hg18)
  require(data.table)
  extdir <- system.file("extdata", package="VanillaICE", mustWork=TRUE)
  features <- suppressWarnings(fread(file.path(extdir, "SNP_info.csv")))
  fgr <- GRanges(paste0("chr", features$Chr), IRanges(features$Position, width=1),
                 isSnp=features[["Intensity Only"]]==0)
  fgr <- SnpGRanges(fgr)
  names(fgr) <- features[["Name"]]
  bsgenome <- BSgenome.Hsapiens.UCSC.hg18
  seqlevels(fgr, pruning.mode="coarse") <- seqlevels(bsgenome)[seqlevels(bsgenome) %in% seqlevels(fgr)]
  seqinfo(fgr) <- seqinfo(bsgenome)[seqlevels(fgr),]
  fgr <- sort(fgr)
  files <- list.files(extdir, full.names=TRUE, recursive=TRUE, pattern="FinalReport")
  ids <- gsub(".rds", "", gsub("FinalReport", "", basename(files)))
  views <- ArrayViews(rowRanges=fgr,
                      sourcePaths=files,
                      sample_ids=ids)
  lrrFile(views)
  ## view of first 10 markers and samples 3 and 5
  views <- views[1:10, c(3,5)]

Function for updating parameters for emission probabilities

Description

This function is not meant to be called directly by the user. It is exported in the package NAMESPACE for internal use by other BioC packages.

Usage

baumWelchUpdate(param, assay_list)

Arguments

param

A container for the HMM parameters

assay_list

list of log R ratios and B allele frequencies


Calculate the emission probabilities for the 6-state HMM

Description

Given the data and an object containing parameters for the HMM, this function computes emission probabilities. This function is not intended to be called by the user and is exported for internal use by other BioC packages.

Usage

calculateEmission(x, param = EmissionParam())

Arguments

x

list of low-level data with two elements: a numeric vector of log R ratios and a numeric vector of B allele frequencies

param

parameters for the 6-state HMM

Value

A matrix of emission probabilities. Column correspond to the HMM states and rows correspond to markers on the array (SNPs and nonpolymorphic markers)

See Also

baumWelchUpdate


A parameter class for computing Emission probabilities

Description

Parameters for computing emission probabilities for a 6-state HMM, including starting values for the mean and standard deviations for log R ratios (assumed to be Gaussian) and B allele frequencies (truncated Gaussian), and initial state probabilities.

This function is exported primarily for internal use by other BioC packages.

Usage

cn_means(object)

cn_sds(object)

baf_means(object)

baf_sds(object)

baf_means(object) <- value

baf_sds(object) <- value

cn_sds(object) <- value

cn_means(object) <- value

EmissionParam(
  cn_means = CN_MEANS(),
  cn_sds = CN_SDS(),
  baf_means = BAF_MEANS(),
  baf_sds = BAF_SDS(),
  initial = rep(1/6, 6),
  EMupdates = 5L,
  CN_range = c(-5, 3),
  temper = 1,
  p_outlier = 1/100,
  modelHomozygousRegions = FALSE
)

EMupdates(object)

## S4 method for signature 'EmissionParam'
show(object)

Arguments

object

see showMethods("EMupdates")

value

numeric vector

cn_means

numeric vector of starting values for log R ratio means (order is by copy number state)

cn_sds

numeric vector of starting values for log R ratio standard deviations (order is by copy number state)

baf_means

numeric vector of starting values for BAF means ordered. See example for details on how these are ordered.

baf_sds

numeric vector of starting values for BAF means ordered. See example for details on how these are ordered.

initial

numeric vector of intial state probabilities

EMupdates

number of EM updates

CN_range

the allowable range of log R ratios. Log R ratios outside this range are thresholded.

temper

Emission probabilities can be tempered by emit^temper. This is highly experimental.

p_outlier

probability that an observation is an outlier (assumed to be the same for all markers)

modelHomozygousRegions

logical. If FALSE (default), the emission probabilities for BAFs are modeled from a mixture of truncated normals and a Unif(0,1) where the mixture probabilities are given by the probability that the SNP is heterozygous. See Details below for a discussion of the implications.

Details

The log R ratios are assumed to be emitted from a normal distribution with a mean and standard deviation that depend on the latent copy number. Similarly, the BAFs are assumed to be emitted from a truncated normal distribution with a mean and standard deviation that depends on the latent number of B alleles relative to the total number of alleles (A+B).

Value

numeric vector

Details

When modelHomozygousRegions is FALSE (the default in versions >= 1.28.0), emission probabilities for B allele frequences are calculated from a mixture of a truncated normal densities and a Unif(0,1) density with the mixture probabilities given by the probability that a SNP is homozygous. In particular, let p denote a 6 dimensional vector of density estimates from a truncated normal distribution for the latent genotypes 'A', 'B', 'AB', 'AAB', 'ABB', 'AAAB', and 'ABBB'. The probability that a genotype is homozygous is estimated as

prHom=(p["A"]+p["B"])/sum(p)prHom=(p["A"] + p["B"])/sum(p)

and the probability that the genotype is heterozygous (any latent genotype that is not 'A' or 'B') is given by

prHet=1prHomprHet = 1-prHom

Since the density of a Unif(0,1) is 1, the 6-dimensional vector of emission probability at a SNP is given by

emit=prHetp+(1prHet)emit = prHet * p + (1-prHet)

The above has the effect of minimizing the influence of BAFs near 0 and 1 on the state path estimated by the Viterbi algorithm. In particular, the emission probability at homozygous SNPs will be virtually the same for states 3 and 4, but at heterozygous SNPs the emission probability for state 3 will be an order of magnitude greater for state 3 (diploid) compared to state 4 (diploid region of homozygosity). The advantage of this parameterization are fewer false positive hemizygous deletion calls. [ Log R ratios tend to be more sensitive to technical sources of variation than the corresponding BAFs/ genotypes. Regions in which the log R ratios are low due to technical sources of variation will be less likely to be interpreted as evidence of copy number loss if heterozygous genotypes have more 'weight' in the emission estimates than homozgous genotypes. ] The trade-off is that only states estimated by the HMM are those with copy number alterations. In particular, copy-neutral regions of homozygosity will not be called.

By setting modelHomozygousRegions = TRUE, the emission probabilities at a SNP are given simply by the p vector described above and copy-neutral regions of homozygosity will be called.#'

Examples

ep <- EmissionParam()
cn_means(ep)
ep <- EmissionParam()
cn_sds(ep)
ep <- EmissionParam()
baf_means(ep)
ep <- EmissionParam()
baf_sds(ep)
ep <- EmissionParam()
baf_means(ep) <- baf_means(ep)
ep <- EmissionParam()
baf_sds(ep) <- baf_sds(ep)
ep <- EmissionParam()
cn_sds(ep) <- cn_sds(ep)
ep <- EmissionParam()
cn_means(ep) <- cn_means(ep)
ep <- EmissionParam()
show(ep)
cn_means(ep)
cn_sds(ep)
baf_means(ep)
baf_sds(ep)

Filter the HMM-derived genomic ranges for copy number variants

Description

The HMM-derived genomic ranges are represented as a GRanges-derived object. cnvFilter returns a GRanges object using the filters stipulated in the filters argument.

Usage

cnvFilter(object, filters = FilterParam())

cnvSegs(object, filters = FilterParam(state = c("1", "2", "5", "6")))

duplication(object, filters = FilterParam(state = c("5", "6")))

deletion(object, filters = FilterParam(state = c("1", "2")))

hemizygous(object, filters = FilterParam(state = "2"))

homozygous(object, filters = FilterParam(state = "1"))

## S4 method for signature 'HMM'
cnvSegs(object, filters = FilterParam(state = as.character(c(1, 2, 5, 6))))

## S4 method for signature 'HMMList'
segs(object)

## S4 method for signature 'HMMList'
hemizygous(object)

## S4 method for signature 'HMMList'
homozygous(object)

## S4 method for signature 'HMMList'
duplication(object)

## S4 method for signature 'HMMList'
cnvSegs(object, filters = FilterParam(state = as.character(c(1, 2, 5, 6))))

## S4 method for signature 'HMMList'
cnvFilter(object, filters = FilterParam())

## S4 method for signature 'HmmGRanges'
cnvSegs(object, filters = FilterParam(state = as.character(c(1, 2, 5, 6))))

Arguments

object

see showMethods(cnvFilter)

filters

a FilterParam object

See Also

FilterParam

Examples

data(snp_exp)
fit <- hmm2(snp_exp)
segs(fit) ## all intervals
cnvSegs(fit)
filter_param <- FilterParam(probability=0.95, numberFeatures=10, state=c("1", "2"))
cnvSegs(fit, filter_param)
filter_param <- FilterParam(probability=0.5, numberFeatures=2, state=c("1", "2"))
cnvSegs(fit, filter_param)
hemizygous(fit)
homozygous(fit)
duplication(fit)

Parameters for parsing source files containing SNP-array processed data, such as GenomeStudio files for the Illumina platform

Description

Raw SNP array processed files have headers and variable labels that may depend the software, how the output files was saved, the software version, and other factors. The purpose of this container is to collect the parameters relevant for reading in the source files for a particular project in a single container. This may require some experimentation as the example illustrates. The function fread in the data.table package greatly simplifies this process.

Usage

CopyNumScanParams(
  cnvar = "Log R Ratio",
  bafvar = "B Allele Freq",
  gtvar = c("Allele1 - AB", "Allele2 - AB"),
  index_genome = integer(),
  select = integer(),
  scale = 1000,
  row.names = 1L
)

## S4 method for signature 'CopyNumScanParams'
show(object)

Arguments

cnvar

length-one character vector providing name of variable for log R ratios

bafvar

length-one character vector providing name of variable for B allele frequencies

gtvar

length-one character vector providing name of variable for genotype calls

index_genome

integer vector indicating which rows of the of the source files (e.g., GenomeStudio) to keep. By matching on a sorted GRanges object containing the feature annotation (see example), the information on the markers will also be sorted.

select

integer vector specifying indicating which columns of the source files to import (see examples)

scale

length-one numeric vector for rescaling the raw data and coercing to class integer. By default, the low-level data will be scaled and saved on disk as integers.

row.names

length-one numeric vector indicating which column the SNP names are in

object

a CopyNumScanParams object

Slots

index_genome

an integer vector

cnvar

the column label for the log R ratios

bafvar

the column label for the B allele frequencies

gtvar

the column label(s) for the genotypes

scale

length-one numeric vector indicating how the low-level data should be scaled prior to saving on disk

select

numeric vector indicating which columns to read

row.names

length-one numeric vector indicating which column the SNP names are in

See Also

ArrayViews parseSourceFile

Examples

CopyNumScanParams() ## empty container

Helper function to determine whether to update the HMM parameters via the Baum-Welch algorithm

Description

This function is not intended to be called directly by the user, and is exported only for internal use by other BioC packages.

Usage

doUpdate(param)

Arguments

param

An object containing parameters for the HMM

See Also

HmmParam


Drop markers on the same chromosome having the same genomic coordinates

Description

If there are multiple markers on the same chromosome with the same annotated position, only the first is kept.

Usage

dropDuplicatedMapLocs(object)

Arguments

object

a container for which the methods seqnames and start are defined

Value

an object of the same class with duplicated genomic positions removed

Examples

data(snp_exp)
g <- rowRanges(snp_exp)
## duplicate the first row
g[length(g)] <- g[1]
 rowRanges(snp_exp) <- g
 snp_exp2 <- dropDuplicatedMapLocs(snp_exp)

Filter sex chromosomes

Description

Removes markers on chromosomes X and Y.

Usage

dropSexChrom(object)

Arguments

object

an object for which the methods seqnames and rowRanges are defined.

Value

an object of the same class as the input


Methods to set and get emission probabilities

Description

Get or set a matrix of emission probabilities. This function is exported primarily for internal use by other BioC packages.

Usage

emission(object)

emission(object) <- value

Arguments

object

see showMethods(emission)

value

a matrix of emission probabilities

Value

matrix


Accessor for parameters used to compute emission probabilities

Description

Parameters for computing emission probabilities include the starting values for the Baum Welch update and initial state probabilities.

Usage

emissionParam(object)

emissionParam(object) <- value

Arguments

object

an object of class EmissionParam

value

an object of class EmissionParam

Value

EmissionParam instance

Examples

hparam <- HmmParam()
emissionParam(hparam)
ep <- EmissionParam()
cn_means(ep) <- log2(c(.1/2, 1/2, 2/2, 2/2, 3/2, 4/2))
emissionParam(hparam) <- ep

Container for the common criteria used to filtering genomic ranges

Description

The maximum a posteriori estimate of the trio copy number state for each genomic range is represented in a GRanges-derived class. Ultimately, these ranges will be filtered based on the trio copy number state (e.g., denovo deletions), size, number of features (SNPs), or chromosome. FilterParam is a container for the parameters commmonly used to filter the genomic ranges.

Usage

FilterParam(
  probability = 0.99,
  numberFeatures = 10,
  seqnames = paste0("chr", c(1:22, "X", "Y")),
  state = as.character(1:6),
  width = 1L
)

## S4 method for signature 'FilterParam'
probability(object)

## S4 method for signature 'FilterParam'
state(object)

## S4 method for signature 'FilterParam'
show(object)

Arguments

probability

minumum probability for the call

numberFeatures

minumum number of SNPs/nonpolymorphic features in a region

seqnames

the seqnames (character string or Rle to keep)

state

character: the HMM states to keep

width

the minimum widht of a region

object

a FilterParam object

Slots

probability

a length-one numeric vector indicating the minimum posterior probability for the called state. Genomic intervals with posterior probabilities below probability will be filtered.

numberFeatures

a positive integer indicating the minimum number of features in a segment

seqnames

a character vector of seqnames to select (i.e., 'chr1' for only those intervals on chromosome 1)

width

positive integer indicating the minimal width of genomic intervals

state

character string indicating which hidden Markov model states to select

See Also

cnvFilter cnvSegs hmm2

Examples

fp <- FilterParam()
width(fp)
numberFeatures(fp)
seqnames(fp)
## To select CNV segments for which
## - the CNV call has a 'posterior' probability of at least 0.95
## - the number of features is at least 10
## - the HMM states are 1 (homozygous deletion) or 2 (hemizygous deletion)
FilterParam(probability=0.95, numberFeatures=10, state=c("1", "2"))

Accessor for HMM filter parameters

Description

Accessor for HMM filter parameters

Usage

filters(object)

Arguments

object

see showMethods(filters)


Accessor for SNP genotypes

Description

Extract SNP genotypes. Genotypes are assumed to be represented as integers: 1=AA, 2=AB, 3=BB.

Usage

genotypes(object)

## S4 method for signature 'ArrayViews'
lrr(object)

## S4 method for signature 'ArrayViews'
baf(object)

## S4 method for signature 'ArrayViews'
genotypes(object)

## S4 method for signature 'SnpArrayExperiment'
baf(object)

## S4 method for signature 'SnpArrayExperiment'
copyNumber(object)

## S4 method for signature 'SnpArrayExperiment'
lrr(object)

## S4 method for signature 'SnpArrayExperiment'
genotypes(object)

Arguments

object

see showMethods("genotypes")

See Also

copyNumber


Create an example SnpArrayExperiment from source files containing marker-level genomic data that are provided in this package

Description

Create an example SnpArrayExperiment from source files containing marker-level genomic data that are provided in this package

Usage

getExampleSnpExperiment(bsgenome)

Arguments

bsgenome

a BSgenome object

Value

A SnpArrayExperiment

Examples

## Not run: 
   if(require("BSgenome.Hsapiens.UCSC.hg18")){
     genome <- BSgenome.Hsapiens.UCSC.hg18
     snp_exp <- getExampleSnpExperiment(genome)
   }

## End(Not run)

Accessor for HMM model parameters

Description

Accessor for HMM model parameters

Usage

getHmmParams(object)

Arguments

object

see showMethods(HmmParam)

Examples

hmm_object <- HMM()
getHmmParams(hmm_object)

Container for the segmented data and the 6-state HMM model parameters

Description

The contructor HMM creates and object of class HMM. Not typically called directly by the user.

Usage

HMM(
  granges = GRanges(),
  param = HmmParam(),
  posterior = matrix(),
  filters = FilterParam()
)

## S4 method for signature 'HMM'
state(object)

## S4 method for signature 'HMM'
show(object)

Arguments

granges

a GRanges object

param

a HmmParam object

posterior

matrix of posterior probabilities

filters

an object of class FilterParam

object

a HMM object

Slots

granges

a GRanges object

param

a HmmParam object

posterior

a matrix of posterior probabilities

filters

a FilterParam object

See Also

hmm2

Examples

data(snp_exp)
hmm_list <- hmm2(snp_exp[,1])
resultsFirstSample <- hmm_list[[1]]
resultsFirstSample
HMM()

Fit a 6-state HMM to log R ratios and B allele frequencies estimated from SNP arrays

Description

This function is intended for estimating the integer copy number from germline or DNA of clonal origin using a 6-state HMM. The states are homozygous deletion, hemizygous deletion, diploid copy number, diploid region of homozygosity, single copy gain, and two+ copy gain. Because heterozygous markers are more informative for copy number than homozygous markers and regions of homozgosity are common in normal genomes, we currently computed a weighted average of the BAF emission matrix with a uniform 0,1 distribution by the probability that the marker is heterozygous, thereby downweighting the contribution of homozygous SNPs to the likelihood. In addition to making the detection of copy-neutral regions of homozgosity less likely, it also helps prevent confusing hemizygous deletions with copy neutral regions of homozygosity – the former would be driven mostly by the log R ratios. This is experimental and subject to change.

Usage

hmm2(
  object,
  emission_param = EmissionParam(),
  transition_param = TransitionParam(),
  ...
)

## S4 method for signature 'SnpArrayExperiment'
hmm2(
  object,
  emission_param = EmissionParam(),
  transition_param = TransitionParam(),
  ...
)

## S4 method for signature 'oligoSnpSet'
hmm2(
  object,
  emission_param = EmissionParam(),
  transition_param = TransitionParam(),
  ...
)

## S4 method for signature 'ArrayViews'
hmm2(
  object,
  emission_param = EmissionParam(),
  transition_param = TransitionParam(),
  tolerance = 2,
  verbose = FALSE,
  ...
)

Arguments

object

A SnpArrayExperiment

emission_param

A EmissionParam object

transition_param

A TransitionParam object

...

currently ignored

tolerance

length-one numeric vector. When the difference in the log-likelihood of the Viterbi state path between successive models (updated by Baum Welch) is less than the tolerance, no additional model updates are performed.

verbose

logical. Whether to display messages indicating progress.

Details

The hmm2 method allows parallelization across samples using the foreach paradigm. Parallelization is automatic when enabled via packages such as snow/doSNOW.

Examples

tp <- TransitionParam()
TransitionParam(taup=1e12)
data(snp_exp)
emission_param <- EmissionParam(temper=1/2)
fit <- hmm2(snp_exp, emission_param)
unlist(fit)
cnvSegs(fit)
## There is too little data to infer cnv reliably in this trivial example.
## To illustrate filtering options on the results, we select
## CNVs for which
## - the CNV call has a posterior probability of at least 0.5
## - the number of features is 2 or more
## - the HMM states are 1 (homozygous deletion) or 2 (hemizygous deletion)
fp <- FilterParam(probability=0.5, numberFeatures=2, state=c("1", "2"))
cnvSegs(fit, fp)
## for parallelization
## Not run: 
   library(snow)
   library(doSNOW)
   cl <- makeCluster(2, type = "SOCK")
   registerDoSNOW(cl)
   fit <- hmm2(snp_exp, emission_param)

## End(Not run)

Constructor for HMMList class

Description

The constructor function for the HMMList class. The constructor is useful for representing a list of HMM objects.

Usage

HMMList(object)

Arguments

object

a list. Each element of the list is in instance of the HMM class.

See Also

HMMList HMM hmm2


Class, constructor, and methods for representing HMM results from multiple samples

Description

Each element of the HMMList contains the genomic intervals of the HMM segmentation (GRanges-derived object), parameters from the Baum-Welch, and a FilterParam object.

Usage

## S4 method for signature 'HMMList'
show(object)

## S4 method for signature 'HMMList'
unlist(x, recursive = TRUE, use.names = TRUE)

Arguments

object

a HMMList object

x

a HMMList object

recursive

logical; currently ignored

use.names

logical; currently ignored

Slots

.Data

a list. Each element of the list should be a HMM object.

See Also

HMM

Examples

data(snp_exp)
fit <- hmm2(snp_exp)
class(fit)
identical(length(fit), ncol(snp_exp))
unlist(fit)

Constructor for HmmParam class

Description

Contains emission probabilities, parameters for emission probabilities, and transition probabilities required for computing the most likely state path via the Viterbi algorithm

Usage

HmmParam(
  emission = matrix(0, 0, 0),
  emission_param = EmissionParam(),
  transition = rep(0.99, nrow(emission)),
  chromosome = character(nrow(emission)),
  loglik = LogLik(),
  viterbi = Viterbi(),
  compute_posteriors = TRUE,
  verbose = FALSE
)

## S4 method for signature 'HmmParam'
show(object)

## S4 method for signature 'HmmParam'
nrow(x)

## S4 method for signature 'HmmParam'
ncol(x)

Arguments

emission

A matrix of emission probabilities

emission_param

an object of class EmissionParam

transition

vector of transition probabilities whose length is N-1, where N is the number of markers. User should provide the probability that the state at marker j is the same as the state at marker j-1. It is assumed that the probability of transitioning to state_j from state_j-1 is the same for all states != state_j-1.

chromosome

character vector

loglik

an object of class LogLik

viterbi

an object of class Viterbi

compute_posteriors

logical

verbose

logical

object

a HmmParam object

x

a HmmParam object

Examples

HmmParam()

Example output from the hidden markov model

Description

The results of a 6-state HMM fit to simulated copy number and genotype data.

Format

a GRanges object


Constructor for HmmTrellisParam class

Description

Constructor for HmmTrellisParam class

Usage

HmmTrellisParam(
  ylimits = list(c(0, 1), c(-3, 1)),
  expandfun = function(g) {     width(g) * 50 }
)

Arguments

ylimits

length-two list of the y-axis limits for B allele frequencies and log R ratios, respectively

expandfun

a function that takes a length-one GRanges object as an argument and computes a width relative to the width of the GRanges object


Constructor for IdiogramParam objects

Description

Parameters for plotting idiograms

Usage

IdiogramParams(
  seqnames = character(),
  seqlengths = numeric(),
  unit = "kb",
  genome = "hg19",
  box = list(color = "blue", lwd = 1)
)

## S4 method for signature 'IdiogramParams,ANY'
plot(x, y, ...)

Arguments

seqnames

length-one character vector providing chromosome name

seqlengths

length-one numeric vector indicating size of chromosome

unit

character string indicating unit for genomic position

genome

character string indicating genome build

box

a list of parameters for plotting the box around the part of the idiogram that is plotted

x

an IdiogramParam object

y

ignored

...

ignored

Value

IdiogramParam object


Paramater class for plotting idiograms

Description

Paramater class for plotting idiograms

Usage

## S4 method for signature 'IdiogramParams'
show(object)

Arguments

object

an IdiogramParam object

Slots

seqnames

length-one character vector providing chromosome name

seqlengths

length-one numeric vector indicating size of chromosome

unit

character string indicating unit for genomic position (default is 'kb')

genome

character string indicating genome build

box

a list of parameters for plotting the box around the part of the idiogram that is plotted.

Examples

if(require(BSgenome.Hsapiens.UCSC.hg18) && require(grid)){
   si <- seqinfo(BSgenome.Hsapiens.UCSC.hg18)
   iparam <- IdiogramParams(seqnames="chr1",
                            genome="hg18",
                            seqlengths=seqlengths(si)["chr1"],
                            box=list(xlim=c(20e6L, 25e6L), color="blue", lwd=2))
   iparam
   idiogram <- plot(iparam)
   vp <- viewport(x=0.05, y=0.8, width=unit(0.9, "npc"), height=unit(0.2, "npc"),
                  name="vp1", just=c("left", "bottom"))
   grid.newpage()
   pushViewport(vp)
   print(idiogram, vp=vp, newpage=FALSE)
}

Assess whether genotype is heterozygous based on BAFs

Description

Assess whether genotype is heterozygous based on BAFs

Usage

isHeterozygous(object, cutoff)

## S4 method for signature 'ArrayViews'
isHeterozygous(object, cutoff)

## S4 method for signature 'SnpArrayExperiment'
isHeterozygous(object, cutoff)

## S4 method for signature 'numeric'
isHeterozygous(object, cutoff)

## S4 method for signature 'matrix'
isHeterozygous(object, cutoff)

Arguments

object

a SnpArrayExperiment or ArrayViews object containing BAFs, a matrix of BAFs, or a numeric vector of BAFs. vector of BAFs

cutoff

a length-two numeric vector providing the range of BAFs consistent with allelic heterozygosity

Examples

if(require("BSgenome.Hsapiens.UCSC.hg18")){
  bsgenome <- BSgenome.Hsapiens.UCSC.hg18
  snp_exp <- getExampleSnpExperiment(bsgenome)
  is_het <- isHeterozygous(snp_exp[, 1], c(0.4, 0.6))
  table(is_het)
}

Constructor for LogLik class

Description

A container for the log likelihood of the Viterbi state path. Stores the log likelihood from succesive updates of model parameters. When the difference between the log likelihoods at iteration i and i-1 is below the tolerance, no additional updates are performed.

Usage

LogLik(loglik = numeric(), tolerance = 1L)

Arguments

loglik

length-one numeric vector for the log likelihood of the Viterbi state path

tolerance

if the difference in the log-likelihood of the Viterbi state path after the Baum-Welch update is less than the specified tolerance, no additional Baum-Welch updates are required

See Also

LogLik


Classes and methods for storing/getting log-likelihoods from Viterbi algorithm

Description

Exported for internal use by other BioC packages

Usage

## S4 method for signature 'LogLik'
length(x)

## S4 method for signature 'LogLik'
show(object)

Arguments

x

object of class LogLik

object

a LogLik object

Slots

loglik

a numeric vector

tolerance

a numeric vector

See Also

LogLik


Accessors for objects of class ArrayViews

Description

Accessors for objects of class ArrayViews

Usage

lrrFile(object)

lrrFile(object) <- value

bafFile(object)

gtFile(object)

## S4 method for signature 'ArrayViews'
lrrFile(object)

## S4 replacement method for signature 'ArrayViews'
lrrFile(object) <- value

## S4 method for signature 'ArrayViews'
bafFile(object)

## S4 method for signature 'ArrayViews'
gtFile(object)

Arguments

object

see showMethods("lrrFile")

value

a character vector of filenames for the log R ratios

Examples

views <- ArrayViews(parsedPath=tempdir())
sourcePaths(views)
lrrFile(views)
bafFile(views)
gtFile(views)

A class allowing matrix or NULL objects

Description

Exported for internal use by other BioC packages


Remove SNPs with NAs in any of the low-level estimates

Description

Remove SNPs with NAs in any of the low-level estimates

Usage

NA_filter(x, i)

Arguments

x

a container for SNP data (SnpArrayExperiment)

i

integer vector to subset

Value

An object of the same class


The number of SNP/nonpolymorphic probes contained in a genomic interval

Description

The number of SNP/nonpolymorphic probes contained in a genomic interval

Usage

numberFeatures(object)

Arguments

object

see showMethods(numberFeatures)


Complete path to directory for keeping parsed files

Description

A character string indicating the complete path for storing parsed files.

Usage

parsedPath(object)

## S4 method for signature 'ArrayViews'
parsedPath(object)

Arguments

object

a ArrayViews object

See Also

parseSourceFile ArrayViews

ArrayViews


Function for parsing GenomeStudio files

Description

This function parses genome studio files, writing the low-level data for log R ratios, B allele frequencies, and genotypes to disk as integers (1 file per subject per data type).

Usage

parseSourceFile(object, param)

## S4 method for signature 'ArrayViews,CopyNumScanParams'
parseSourceFile(object, param)

Arguments

object

An ArrayViews object

param

An object of class CopyNumScanParams

See Also

ArrayViews ArrayViews CopyNumScanParams

Examples

require(BSgenome.Hsapiens.UCSC.hg18)
  bsgenome <- BSgenome.Hsapiens.UCSC.hg18
  require(data.table)
  extdir <- system.file("extdata", package="VanillaICE", mustWork=TRUE)
  features <- suppressWarnings(fread(file.path(extdir, "SNP_info.csv")))
  fgr <- GRanges(paste0("chr", features$Chr), IRanges(features$Position, width=1),
                 isSnp=features[["Intensity Only"]]==0)
  fgr <- SnpGRanges(fgr)
  names(fgr) <- features[["Name"]]
  seqlevels(fgr) <- seqlevels(bsgenome)[seqlevels(bsgenome) %in% seqlevels(fgr)]
  seqinfo(fgr) <- seqinfo(bsgenome)[seqlevels(fgr),]
  fgr <- sort(fgr)
  files <- list.files(extdir, full.names=TRUE, recursive=TRUE, pattern="FinalReport")
  views <- ArrayViews(rowRanges=fgr, sourcePaths=files, parsedPath=tempdir())
  show(views)

## read the first file
dat <- fread(files[1], skip="[Data]")
## information to store on the markers
select <- match(c("SNP Name", "Allele1 - AB", "Allele2 - AB",
                  "Log R Ratio", "B Allele Freq"), names(dat))
##
## which rows to keep in the MAP file. By matching on the sorted GRanges object
## containing the feature annotation, the low-level data for the log R ratios/
## B allele frequencies will also be sorted
##
index_genome <- match(names(fgr), dat[["SNP Name"]])
scan_params <- CopyNumScanParams(index_genome=index_genome, select=select)
##
## parse the source files
##
parseSourceFile(views, scan_params)
list.files(parsedPath(views))
##
##  Inspecting source data through accessors defined on the views object
##
require(oligoClasses)
## log R ratios
r <- head(lrr(views))
## B allele frequencies
b <- head(baf(views))
g <- head(genotypes(views))

Accessor for probability filter

Description

Accessor for probability filter

Usage

probability(object)

Arguments

object

a FilterParam object


Rescale a numeric vector

Description

Rescale a numeric vector

Usage

rescale(x, l, u)

Arguments

x

numeric vector

l

lower limit of rescaled x

u

upper limit of rescaled x


Robust statistics for matrices

Description

Compute the column-wide or row-wise mode of numeric matrices

Usage

rowModes(x)

colModes(x)

rowMAD(x, ...)

Arguments

x

matrix

...

additional arguments to rowMedians

Value

numeric vector

See Also

mad

mad rowMedians

Examples

X <- matrix(rnorm(100), 10, 10)
rowMAD(X)

Accessor for the HMM segments

Description

Accessor to obtain all segments from the HMM.

Usage

segs(object)

Arguments

object

see showMethods(segs)

Value

a GRanges-derived object


Show method for objects of class Viterbi

Description

Show method for objects of class Viterbi

Usage

## S4 method for signature 'Viterbi'
show(object)

Arguments

object

a Viterbi object


An example SnpArrayExperiment

Description

A container for low-level summaries used for downstream copy number estimation, including log R ratios, B allele frequencies, and genotypes

Format

a SnpArrayExperiment object


Create an assays object from log R ratios and B allele frequencies

Description

This function is exported primarily for internal use by other BioC packages.

Usage

snpArrayAssays(cn = new("matrix"), baf = new("matrix"), ...)

Arguments

cn

matrix of log R ratios

baf

matrix of B allele frequencies

...

additional matrices of the same dimension, such as SNP genotypes.

Examples

data(snp_exp, package="VanillaICE")
r <- lrr(snp_exp)
b <- baf(snp_exp)
sl <- snpArrayAssays(cn=r, baf=b)

A RangedSummarizedExperiment-derived class of marker-level SNP array data for copy number inference

Description

Constructor for SnpArrayExperiment

Usage

SnpArrayExperiment(
  cn,
  baf,
  rowRanges = GRanges(),
  colData = DataFrame(),
  isSnp = logical(),
  ...
)

## S4 method for signature 'missing'
SnpArrayExperiment(
  cn,
  baf,
  rowRanges = GRanges(),
  colData = DataFrame(),
  isSnp = logical(),
  ...
)

## S4 method for signature 'matrix'
SnpArrayExperiment(
  cn,
  baf,
  rowRanges = GRanges(),
  colData = DataFrame(row.names = colnames(cn)),
  isSnp = logical(),
  ...
)

Arguments

cn

matrix of copy number estimates (e.g., log R ratios)

baf

matrix of B allele frequencies

rowRanges

GRanges object for SNPs/nonpolymorphic markers

colData

DataFrame containing sample-level covariates

isSnp

logical vector indicating whether marker is a SNP

...

additional arguments passed to SummarizedExperiment() constructor function

Examples

## empty container
library(VanillaICE)
data(snp_exp, package="VanillaICE") # example

se <- SnpArrayExperiment(cn=lrr(snp_exp), baf=baf(snp_exp),
                   rowRanges=rowRanges(snp_exp))

Constructor for SnpArrayExperiment

Description

A single-argument generic function to construct a SnpArrayExperiment.

Usage

SnpExperiment(object)

## S4 method for signature 'ArrayViews'
SnpExperiment(object)

Arguments

object

see showMethods('SnpExperiment') for a list of supported objects

Examples

view <- ArrayViews()
SnpExperiment(view)

An extension to GRanges for representing SNPs

Description

An extension to GRanges for representing SNPs

Constructor for SnpGRanges class

Usage

SnpGRanges(object = GRanges(), isSnp, ...)

## S4 method for signature 'missing'
SnpGRanges(object, isSnp)

## S4 method for signature 'GRanges'
SnpGRanges(object, isSnp)

Arguments

object

A GRanges object

isSnp

A logical vector. Each genomic interval in the GRanges container corresponds to a marker on the genotyping array. isSnp is FALSE for nonpolymorphic markers such as those included on the Affymetrix 6.0 chips.

...

ignored

Slots

elementMetadata

a SnpDataFrame

Examples

SnpGRanges()
g <- GRanges("chr1", IRanges(15L, 15L))
SnpGRanges(g, isSnp=TRUE)

Accessor for file paths containing SNP-level summaries

Description

Files containing SNP-level summaries for log R ratios, B allele frequencies, and genotypes – one sample per subject – are required.

Usage

sourcePaths(object)

Arguments

object

an ArrayViews object

Examples

sourcePaths(ArrayViews())

Retrieve genomic location of SNPs

Description

Retrieve genomic location of SNPs

Usage

## S4 method for signature 'oligoSnpSet'
start(x)

Arguments

x

a oligoSnpSet object


Accessor for the Viterbi state path

Description

The states are represented as integers: 1=homozygous deletion, 2=hemizygous deletion, 3=diploid normal heterozygosity, 4=diploid region of homozygosity, 5=single copy gain, 6=two or more copy gain.

Usage

## S4 method for signature 'Viterbi'
state(object)

Arguments

object

a Viterbi object


Accessor for copy number state

Description

Extract the copy number state for each genomic interval.

Usage

## S4 method for signature 'HmmGRanges'
state(object)

Arguments

object

a HmmGRanges object


Sweep the modal log R ratio (by row or column) from a matrix of log R ratios

Description

This function simplifies the process of sweeping the modal log R ratio from the rows or columns of a SnpArrayExperiment object. It is most useful when a large number of samples (more than 10) are available and the dataset is a collection of germline samples. We assume that the samples are from a single batch and that the modal value will be a robust estimate of the mean log R ratio for diploid copy number. Variation in the modal estimates between markers is presumed to be attributable to probe effects (e.g., differences hybridization efficiency/PCR do to sequence composition). For sex chromosomes, one should apply this function separately to men and women and then recenter the resulting matrix according to the expected copy number.

Usage

sweepMode(x, MARGIN)

## S4 method for signature 'SnpArrayExperiment'
sweepMode(x, MARGIN)

Arguments

x

see showMethods(sweepMode)

MARGIN

integer indicating which margin (1=rows, 2=columns) to sweep the mode

Value

an object of the same class as x

Examples

data(snp_exp)
snp_exp_rowcentered <- sweepMode(snp_exp, 1)
snp_exp_colcentered <- sweepMode(snp_exp, 2)
x <- lrr(snp_exp)
x_rowcentered <- sweep(x, 1, rowModes(x))
all.equal(lrr(snp_exp_rowcentered), x_rowcentered)

Threshold numeric values

Description

Threshold numeric values according to user-specific limits. The thresholded values can also be jittered near the limits.

Usage

threshold(x, lim = c(-Inf, Inf), amount = 0)

Arguments

x

numeric matrix or vector

lim

limit at which to threshold entries in x

amount

see jitter

See Also

jitter

Examples

x <- rnorm(1000, 0, 3)
y <- threshold(x, c(-5,5))
range(y)

Constructor for TransitionParam class

Description

Contains parameters for computing transition probabilities

Usage

TransitionParam(taup = 1e+10, taumax = 1 - 5e+06)

## S4 method for signature 'TransitionParam'
show(object)

Arguments

taup

length-one numeric vector

taumax

The maximum probability that the current state is the same as the preceding state. See details

object

a TransitionParam object

Details

Diagonal elements of the transition probability matrix are computed as e^-2*d/taup, where d is the distance between markers i and i-1 and taup is typically in the range of 1xe10. This probability is constrained to be no larger than taumax. The probabilities on the off-diagonal elements are the same and are subject to the constraint that the rows of the transition probability matrix sum to 1.

Examples

TransitionParam()
## higher values of taup make transitions between states less likely
TransitionParam(taup=1e12)

Run the Baum-Welch algorithm to update HMM parameters

Description

This function is not intended to be called directly by the user. It is exported in the package NAMESPACE for internal use by other BioC packages.

Usage

updateHmmParams(
  object,
  emission_param = EmissionParam(),
  transition_param = TransitionParam()
)

Arguments

object

a SnpArrayExperiment object

emission_param

a EmissionParam object

transition_param

a TransitionParam object


Default viewports for plotting CNV data with lattice-style graphics

Description

Default viewports for plotting CNV data with lattice-style graphics

Usage

viewports()

Value

list

See Also

xyplotList xygrid

Examples

vps <- viewports()

Lattice-style plots for granges and SnpArrayExperiment objects

Description

Data for the graphic is generated by a call to grangesData.

Usage

xyplotList(granges, se, param = HmmTrellisParam())

## S4 method for signature 'HmmGRanges,SnpArrayExperiment'
xyplotList(granges, se, param = HmmTrellisParam())

## S4 method for signature 'GRangesList,SnpArrayExperiment'
xyplotList(granges, se, param = HmmTrellisParam())

xygrid(trellis_plot, viewports, granges)

Arguments

granges

a HmmGRanges object

se

a SnpArrayExperiment

param

trellis parameters for plotting HMM

trellis_plot

an object of class trellis

viewports

a list of viewports as provided by the viewports function

See Also

viewports

Examples

if(require("BSgenome.Hsapiens.UCSC.hg18")){
  bsgenome <- BSgenome.Hsapiens.UCSC.hg18
  snp_exp <- getExampleSnpExperiment(bsgenome)
  seqlevels(snp_exp, pruning.mode="coarse") <- "chr22"
  fit <- hmm2(snp_exp)
  g <- reduce(hemizygous(fit), min.gapwidth=500e3)
  trellis_param <- HmmTrellisParam()
  fig <- xyplotList(g, snp_exp, trellis_param)
  vps <- viewports()
  xygrid(fig[[1]], vps, g)
}