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% Generated by roxygen2: do not edit by hand
% Please edit documentation in R/calculate_lesion_segretation.R
\name{calculate_lesion_segregation}
\alias{calculate_lesion_segregation}
\title{Calculate the amount of lesion segregation for a GRangesList or GRanges object.}
\usage{
calculate_lesion_segregation(
vcf_list,
sample_names,
test = c("binomial", "wald-wolfowitz", "rl20"),
split_by_type = FALSE,
ref_genome = NA,
chromosomes = NA
)
}
\arguments{
\item{vcf_list}{GRangesList or GRanges object}
\item{sample_names}{The name of the sample}
\item{test}{The statistical test that should be used. Possible values:
* 'binomial' Binomial test based on the number of strand switches. (Default);
* 'wald-wolfowitz' Statistical test that checks if the strands are randomly distributed.;
* 'rl20' Calculates rl20 value and the genomic span of the associated runs set.;}
\item{split_by_type}{Boolean describing whether the lesion
segregation should be calculated for all SNVs together or per 96 substitution context. (Default: FALSE)}
\item{ref_genome}{BSgenome reference genome object.
Only needed when split_by_type is TRUE with the binomial test
or when using the rl20 test.}
\item{chromosomes}{The chromosomes that are used. Only needed when using the rl20 test.}
}
\value{
A tibble containing the amount of lesions segregation per sample
}
\description{
This function calculates lesion segregation for a GRangesList or GRanges object.
Lesion segregation is a large scale Watson versus Crick strand asymmetry caused by
many DNA lesions occurring during a single cell cycle.
It was first described in Aitken et al., 2020, Nature.
See their paper for a more in-depth discussion of this phenomenon.
This function can perform three different types of test to calculate lesion segregation.
The first method is unique to this package, while the other two were also used by
Aitken et al., 2020.
The 'binomial' test is based on how often consecutive mutations are on different strands.
The 'wald-wolfowitz' test checks if the strands are randomly distributed. It's not known
which method is superior.
The 'rl20' test looks at run sizes (The number of consecutive mutations on the same strand).
This is less susceptible to local strand asymetries and kataegis, but doesn't generate a p-value.
}
\details{
The amount of lesion segregation is calculated per GRanges object.
The results are then combined in a table.
It's possible to calculate the lesion segregation separately per 96 substitution context,
when using the binomial test. The results are then automatically added back up together.
This can increase sensitivity when a mutational process causes multiple types of base substitutions,
which aren’t considered to be on the same strand.
When using the rl20 test, this function first calculates the strand runs per chromosome
and combines them. It then calculates the smallest set of runs, which together encompass
at least 20 percent of the mutations. (This set thus contains the largest runs).
The size of the smallest run in this set is the rl20. The genomic span of
the runs in this set is also calculated.
}
\examples{
## See the 'read_vcfs_as_granges()' example for how we obtained the
## following data:
grl <- readRDS(system.file("states/read_vcfs_as_granges_output.rds",
package = "MutationalPatterns"
))
## To reduce the runtime we take only the first two samples
grl <- grl[1:2]
## Set the sample names
sample_names <- c("colon1", "colon2")
## Load the corresponding reference genome.
ref_genome <- "BSgenome.Hsapiens.UCSC.hg19"
library(ref_genome, character.only = TRUE)
## Calculate lesion segregation
lesion_segretation <- calculate_lesion_segregation(grl, sample_names)
## Calculate lesion segregation per 96 base type
lesion_segretation_by_type <- calculate_lesion_segregation(grl, sample_names,
split_by_type = TRUE, ref_genome = ref_genome
)
## Calculate lesion segregation using the wald-wolfowitz test.
lesion_segregation_wald <- calculate_lesion_segregation(grl,
sample_names,
test = "wald-wolfowitz"
)
## Calculate lesion segregation using the rl20.
chromosomes <- paste0("chr", c(1:22, "X"))
lesion_segregation_rl20 <- calculate_lesion_segregation(grl,
sample_names,
test = "rl20",
ref_genome = ref_genome,
chromosomes = chromosomes
)
}
\seealso{
\code{\link{plot_lesion_segregation}}
Other Lesion_segregation:
\code{\link{plot_lesion_segregation}()}
}
\concept{Lesion_segregation}
|
