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norm.pickrell <- function(counts, x, sizeFactors = NULL, verbose = FALSE){
## Normaliztion as described in Pickrell et al (Nature, 2010)
## Notation as in the supplementary material, page 10
## x : GC content
## counts : a count matrix
bin.gc <- cut(x, unique(c(-1, quantile(x, seq(0.005, 1, 0.005)))))
s <- apply(counts, 2, function(xx) tapply(xx, bin.gc, sum))
f1 <- pmax(s, 0.5) / rowSums(s)
if(is.null(sizeFactors)) {
f0 <- colSums(s) / sum(s)
} else {
f0 <- sizeFactors / sum(sizeFactors)
}
f <- log2(f1) - log2(f0)
bin.meangc <- tapply(x, bin.gc, mean)
offset <- apply(f, 2, function(xx) {
if(verbose) cat(".")
fit1 <- smooth.spline(bin.meangc, xx)
offset <- predict(fit1, x)$y
offset
}) ## This is \hat{g}_{ij}
list(yc = counts * 2^(-offset), offset = offset)
}
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