Linear mixed model confidence intervals

Fit linear mixed model to estimate contribution of multiple sources of variation while simultaneously correcting for all other variables. Then perform parametric bootstrap sampling to get a 95% confidence intervals for each variable for each gene.

Usage

varPartConfInf(
  exprObj,
  formula,
  data,
  REML = FALSE,
  useWeights = TRUE,
  control = vpcontrol,
  nsim = 1000,
  ...
)

Arguments

exprObj

matrix of expression data (g genes x n samples), or ExpressionSet, or EList returned by voom() from the limma package

formula

specifies variables for the linear (mixed) model. Must only specify covariates, since the rows of exprObj are automatically used as a response. e.g.: ~ a + b + (1|c)

data

data.frame with columns corresponding to formula

REML

use restricted maximum likelihood to fit linear mixed model. default is FALSE. Strongly discourage against changing this option, but here for compatibility.

useWeights

if TRUE, analysis uses heteroskedastic error estimates from voom(). Value is ignored unless exprObj is an EList from voom() or weightsMatrix is specified

control

control settings for lmer()

nsim

number of bootstrap datasets

...

Additional arguments for lmer() or lm()

Value

list() of where each entry is the result for a gene. Each entry is a matrix of the 95% confidence interval of the variance fraction for each variable

Details

A linear mixed model is fit for each gene, and bootMer() is used to generate parametric bootstrap confidence intervals. use.u=TRUE is used so that the \(\hat{u}\) values from the random effects are used as estimated and are not re-sampled. This gives confidence intervals as if additional data were generated from these same current samples. Conversely, use.u=FALSE assumes that this dataset is a sample from a larger population. Thus it simulates \(\hat{u}\) based on the estimated variance parameter. This approach gives confidence intervals as if additional data were collected from the larger population from which this dataset is sampled. Overall, use.u=TRUE gives smaller confidence intervals that are appropriate in this case.

Examples

# load library
# library(variancePartition)

library(BiocParallel)

# load simulated data:
# geneExpr: matrix of gene expression values
# info: information/metadata about each sample
data(varPartData)

# Specify variables to consider
# Age is continuous so we model it as a fixed effect
# Individual and Tissue are both categorical, so we model them as random effects
form <- ~ Age + (1 | Individual) + (1 | Tissue)

# Compute bootstrap confidence intervals for each variable for each gene
resCI <- varPartConfInf(geneExpr[1:5, ], form, info, nsim = 100)
#> Warning: Model failed for 1 responses.
#>   See errors with attr(., 'errors')