\name{RPA.pointestimate} \Rdversion{1.1} \alias{RPA.pointestimate} \title{Computing point estimate for the model parameters for all probe sets.} \description{Computes point estimate} \usage{RPA.pointestimate(abatch, sets = NULL, myseed = 101, priors = NULL, epsilon = 1e-2, cind = 1, sigma2.method = "robust", d.method = "fast", verbose = TRUE, bg.method = "rma", normalization.method = "quantiles.robust", cdf = NULL, alpha = NULL, beta = NULL)} \arguments{ \item{abatch }{An AffyBatch object.} \item{sets }{Specifies the probesets for which RPA estimates will be computed. Default: all probe sets.} \item{myseed }{Specifies the random seed.} \item{priors }{An 'rpa.priors' object. Can be used to set user-specified priors for the model parameters. Not applicable for sigma2.method = "var".} \item{epsilon }{Convergence tolerance. The iteration is deemed converged when the change in the d parameter is < epsilon.} \item{cind }{Specifies which array in abatch is used as a reference in computing probe-level differential expression.} \item{sigma2.method }{ Optimization method for sigma2 (probe-specific variances). "robust": (default) update sigma2 by posterior mean, regularized by informative priors that are identical for all probes (user-specified by setting scalar values for alpha, beta). This regularizes the solution, and avoids overfitting where a single probe obtains infinite reliability. This is a potential problem in the other sigma2 update methods with non-informative variance priors. The default values alpha = 2; beta = 1 are used if alpha and beta are not specified. "mode": update sigma2 with posterior mean "mean": update sigma2 with posterior mean "var": update sigma2 with variance around d. Applies the fact that sigma2 cost function converges to variance with large sample sizes. } \item{d.method }{ Method to optimize d. "fast": (default) weighted mean over the probes, weighted by probe variances The solution converges to this with large sample size. "basic": optimization scheme to find a mode used in Lahti et al. TCBB/IEEE; relatively slow; this is the preferred method with small sample sizes. } \item{verbose }{ Print progress information during computation. Default: TRUE.} \item{bg.method }{ Specify background correction method. Default: "rma". See bgcorrect.methods() for other options.} \item{normalization.method }{ Specify quantile normalization method. Default: "pmonly". See normalize.methods(Dilution) for other options.} \item{cdf }{ Specify an alternative CDF environment. Default: none. } \item{alpha, beta }{Prior parameters for inverse Gamma distribution of probe-specific variances. Noninformative prior is obtained with alpha, beta -> 0. Not used with sigma2.method 'var'. Scalar alpha and beta specify an identical inverse Gamma prior for all probes, which regularizes the solution. Probe-specific priors can be set with the 'priors' parameter.} } \details{Calculates RPA estimates of probe reliability and differential expression between the user-specified reference array (cind) and the other arrays in the data set. The model assumes P observations for each transcript target (i.e. a probeset) with Gaussian noise which is specific for each probe (variance is specified by sigma2). The mean (affinity) parameters of the Gaussian noise model cancel out in calculating probe-level differential expression. RPA.pointestimate gives a point estimate for d and sigma2. The 'prior' parameter is not applicable with sigma2.method = "var". The d.method = "fast" is recommended with large sample size.} \value{ An instance of class 'rpa'. This is an extended list containing the following elements: \item{d }{A matrix of probesets x arrays. Specifies the estimated 'true' underlying differential gene expression signal over the arrays (vs. the reference array 'cind') for each investigated probeset. Note that the reference array is not included.} \item{sigma2 }{A list. Each element corresponds to a probeset, and contains a vector that gives the estimated variance for each probe in that probeset.} \item{cind }{Specifies which of the arrays in the abatch (the affybatch object to be analyzed) has been used as the reference for computing probe-level differential expression.} \item{sets }{A character vector listing the investigated probesets.} } \references{Probabilistic Analysis of Probe Reliability in Differential Gene Expression Studies with Short Oligonucleotide Arrays. Lahti et al., TCBB/IEEE, to appear. See http://www.cis.hut.fi/projects/mi/software/RPA/ } \author{Leo Lahti } \note{sigma2.method = "robust" and d.method = "fast" are recommended. With small sample size and informative priors, d.method = "basic" may be preferable.} \seealso{rpa.plot, rpa, set.priors, RPA.preprocess, AffyBatch} \examples{ ## Load example data set #require(affydata) #data(Dilution) ## Compute RPA for whole data set ## ... slow, not executed here # rpa.results <- RPA.pointestimate(Dilution) ## Visualize the results for one of the probe sets #rpa.plot(set, rpa.results) } \keyword{ methods }