Fit, pool and permute a DMSA set test under a declared design

Usage

dmsa_fit(
  data,
  probes,
  alignment,
  design,
  method = c("expected", "fixed"),
  B = 999L,
  engine = c("auto", "lm", "lmer"),
  beta_input = TRUE,
  check = TRUE,
  seed = NULL
)

Arguments

data: data.frame with one row per observation.
probes: Character vector of methylation columns, in the SAME order as the rows of alignment.
alignment: A dmsa_align() result.
design: A dmsa_design() (see alpha_design()).
method: "expected" (certainty-weighted) or "fixed".
B: Permutations. 0 skips the permutation (descriptive only).
engine: "auto" reports from lmer when the design declares random effects and lme4 is installed, otherwise lm. The permutation null is ALWAYS built with the matched lm, and the observed lm statistic is the one compared to it - mixing estimators between observed and null is the classic way to manufacture significance. The agreement between the two is returned.
beta_input: If TRUE (default) probes hold beta values and are converted to M; set FALSE if they are already M.
check: Run dmsa_check_design() first (default TRUE).
seed: Optional integer for reproducible permutation.

Value

An object of class dmsa_fit.

Examples

set.seed(1)
n <- 80; K <- 6; x <- rnorm(n); d <- sample(c(-1, 1), K, TRUE)
M <- matrix(rnorm(n * K), n, K) + outer(x, 0.5 * d)
dat <- data.frame(cID = rep(1:40, each = 2), chip = rep(1:10, each = 8),
                  x = x, sex_c = rep(c(-0.5, 0.5), 40))
probes <- paste0("cg", 1:K); dat[probes] <- 1 / (1 + 2^(-M))
al <- dmsa_align(data.frame(cpg = probes, d = d,
                            p_plus = ifelse(d > 0, 0.95, 0.05)),
                 genes = rep(c("g1", "g2"), each = 3))
des <- dmsa_design("x", "sex_c", random = c("chip", "cID"),
                   exchangeable = "cID")
dmsa_fit(dat, probes, al, des, B = 99, engine = "lm", seed = 1)
#> DMSA set test (expected-sign)
#>   focal x   n = 80   probes 6 used of 6
#>   estimate 0.4768  se 0.0529  z 9.01
#>   permutation p = 0.01  (B = 99, block = cID, z_null-matched = 9.01)
#>   engine lm