tests/testthat/test_betaFitting.R

In DESeq2: Differential gene expression analysis based on the negative binomial distribution

context("betaFitting")
test_that("estimates of beta fit from various methods are equal", {
  # test for equivalence of DESeq2 estimates with those
  # found using IRLS code and using optim
  m <- 10
  set.seed(1)
  y <- rpois(m,20)
  sf <- rep(1,m)
  condition <- factor(rep(0:1,each=m/2))
  x <- cbind(rep(1,m),rep(0:1,each=m/2))
  lambda <- 2
  alpha <- .5

  dds <- DESeqDataSetFromMatrix(matrix(y,nrow=1),
                                colData=DataFrame(condition),
                                design= ~ condition)
  sizeFactors(dds) <- sf
  dispersions(dds) <- alpha
  mcols(dds)$baseMean <- mean(y)

  # for testing we convert beta to the naturual log scale:
  # convert lambda from log to log2 scale by multiplying by log(2)^2
  # then convert beta back from log2 to log scale by multiplying by log(2)
  betaDESeq <- log(2)*DESeq2:::fitNbinomGLMs(dds, lambda=c(0,lambda*log(2)^2))$betaMatrix

  # the IRLS algorithm
  betaIRLS <- c(1,1)
  for (t in 1:100) {
    mu.hat <- as.vector(sf * exp(x %*% betaIRLS))
    w <- diag(1/(1/mu.hat^2 * ( mu.hat + alpha * mu.hat^2 )))
    z <- log(mu.hat/sf) + (y - mu.hat)/mu.hat
    ridge <- diag(c(0,lambda))
    betaIRLS <- as.vector(solve(t(x) %*% w %*% x + ridge) %*% t(x) %*% w %*% z)
  }

  # using optim
  objectiveFn <- function(p) {
    mu <- exp(x %*% p)
    logLike <- sum(dnbinom(y, mu=mu, size=1/alpha, log=TRUE))
    prior <- dnorm(p[2], 0, sqrt(1/lambda),log=TRUE)
    -1 * (logLike + prior)
  }
  betaOptim <- optim(c(.1,.1), objectiveFn, control=list(reltol=1e-16))$par

  expect_equal(as.numeric(betaDESeq), betaIRLS, tolerance=1e-6)
  expect_equal(as.numeric(betaDESeq), betaOptim, tolerance=1e-6)
})