[BioC] VariantTools callVariants - binomial likelihood ratio

[heyi xiao]

Hi,
I try to use VariantTools package package and I am working on the vignette examples. I have some questions on the variant calling procedure. The vignette says: “The callVariants function uses a binomial likelihood ratio test for this purpose. The ratio is P(D|p = plower)=P(D|p = perror).”

To understand this statement, I located the two internal functions that carry out this step.

> VariantTools:::lrtFreqCutoff
function (p0, p1, n = if (C == 1L) 1L else n, C = 1L)
{   
    num <- (1/n) * log(C) + log(1 - p0) - log(1 - p1)
    denom <- log(p1) - log(p0) + log(1 - p0) - log(1 - p1)
    num/denom
}

> VariantTools:::BinomialLRFilter
function (p.lower = 0.2, p.error = 1/1000)
{   
    function(x) {
        freq.cutoff <- lrtFreqCutoff(p.error, p.lower)
        sample.freq <- altDepth(x)/totalDepth(x)
        passed <- sample.freq >= freq.cutoff
        passed[is.na(passed)] <- FALSE
        passed
    }
}

However, I get even more confused. Here are my questions:
The binomial likelihood ratio should be p1^k*(1-p1)^(n-k)/(p0^k*(1-p0)^(n-k)), here n and k are total trial and number of hits. I don’t understand why it becomes num/denom in the lrtFreqCutoff function?

What’s n and C in lrtFreqCutoff? These arguments are not used when BinomialLRFilter calls lrtFreqCutoff, why?

In BinomialLRFilter, the criterion used is sample.freq >= freq.cutoff. But sample.freq <- altDepth(x)/totalDepth(x) is a frequency as defined, yet freq.cutoff seems to be the binomial likelihood ratio. How a frequency can be compared to likelihood ratio?

In BinomialLRFilter, p0=perror = 0.001 and p1=plower = 0.2, the default p0 and p1 values are assumed, why not used the actual sequencing error rate and lowest variant frequency?

Hope someone can explain these problems to me. Thank you!