BMIQ {wateRmelon} | R Documentation

## Beta-Mixture Quantile (BMIQ) Normalisation method for Illumina 450k arrays

### Description

BMIQ is an intra-sample normalisation procedure, correcting the bias of type-2 probe values. BMIQ uses a 3-step procedure: (i) fitting of a 3-state beta mixture model, (ii) transformation of state-membership probabilities of type2 probes into quantiles of the type1 distribution, and (iii) a conformal transformation for the hemi-methylated probes. Exact details can be found in the reference below.

### Usage

    BMIQ(beta.v, design.v, nL = 3, doH = TRUE, nfit = 50000, th1.v = c(0.2, 0.75), th2.v = NULL, niter = 5, tol = 0.001, plots = TRUE, sampleID = 1, pri=TRUE)
    ## S4 method for signature 'MethyLumiSet'
    BMIQ(beta.v, nL=3, doH=TRUE, nfit=5000, th1.v=c(0.2,0.75), th2.v=NULL, niter=5, tol=0.001, plots=FALSE,  pri=FALSE )
    CheckBMIQ(beta.v, design.v, pnbeta.v)

### Arguments

`beta.v` | vector consisting of beta-values for a given sample, or a MethyLumiSet or MethylSet containing multiple samples. For the MethyLumiSet and MethylSet methods, this is the only required argument, and the function will be run on each sample.
`design.v` | corresponding vector specifying probe design type (1=type1,2=type2). This must be of the same length as beta.v and in the same order.
`nL` | number of states in beta mixture model. 3 by default. At present BMIQ only works for nL=3.
`doH` | perform normalisation for hemimethylated type2 probes. These are normalised using an empirical conformal transformation and also includes the left-tailed type2 methylated probes since these are not well described by a beta distribution. By default TRUE.
`nfit` | number of probes of a given design type to use for the fitting. Default is 50000. Smaller values (~10000) will make BMIQ run faster at the expense of a small loss in accuracy. For most applications, 5000 or 10000 is ok.
`th1.v` | thresholds used for the initialisation of the EM-algorithm, they should represent buest guesses for calling type1 probes hemi-methylated and methylated, and will be refined by the EM algorithm. Default values work well in most cases.
`th2.v` | thresholds used for the initialisation of the EM-algorithm, they should represent buest guesses for calling type2 probes hemi-methylated and methylated, and will be refined by the EM algorithm. By default this is null, and the thresholds are estimated based on th1.v and a modified PBC correction method.
`niter` | maximum number of EM iterations to do. This number should be large enough to yield good fits to the type1 distribution. By default 5.
`tol` | tolerance convergence threshold for EM algorithm. By default 0.001.
`plots` | logical specifying whether to plot the fits and normalised profiles out. By default TRUE.
`sampleID` | the ID of the sample being normalised.
`pri` | logical: print verbose progress information?
`pnbeta.v` | BMIQ normalised profile.

### Details

Full details can be found in the reference below. Note: these functions require the RPMM package, not currently a dependency of the wateRmelon package.

### Value

Default method: A list with following entries:

`nbeta` | the normalised beta-profile for the sample
`class1` | the assigned methylation state of type1 probes
`class2` | the assigned methylation state of type2 probes
`av1` | the mean beta-values for the nL states for type1 probes
`av2` | the mean beta-values for the nL states for type2 probes
`hf` | the estimated "Hubble" dilation factor used in the normalisation of hemi-methylated probes
`th1` | estimated thresholds for calling unmethylated and methylated type1 probes
`th2` | estimated thresholds for calling unmethylated and methylated type2 probes

MethyLumiSet method: A methyLumiSet object

### Author(s)

Andrew Teschendorff, MethyLumiSet method by Leo Schalkwyk Leonard.Schalkwyk@kcl.ac.uk

### References

Teschendorff AE, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D, Beck S. A Beta-Mixture Quantile Normalisation method for correcting probe design bias in Illumina Infinium 450k DNA methylation data. Bioinformatics. 2012 Nov 21.

### Examples

    library(RPMM)
    data(melon)
    BMIQ(melon,nfit=100)

[Package wateRmelon version 1.22.1 Index]