ClusteredMutations (version 1.0.2)

features: Describe the features of mutation in the hyper-mutated zones.

Description

Several features were observed in the hyper-mutated zones, for example, kataegis is the proposed name for the hyper-mutated zones with a cluster of C>T and/or C>G mutations that are substantially enriched at TpCpN trinucleotides, on the same DNA strand and that co-localize with large-scale genomic structural variation (Alexandrov et al. 2013; Nik-Zainal et al. 2012).

Usage

features(data = NULL, chr = NULL, position, refbase, mutantbase,
						 min = 6, max = 5000)

Value

features() returns a data set with all mutations in the hyper-mutated zones. The data set contains five variables:

clustered

: number of cluster.

chr

: chromosome.

position

: the position of mutation in the chromosome.

ref_base

: reference base in the chromosome.

mutant_base

: the mutant base in the chromosome.

Arguments

data

: somatic substitution mutations of the cancer genome data set.

chr

: chromosome where the somatic mutation is located.

position

: position of somatic mutations in the DNA sequence of the cancer genome.

refbase

: reference base in the chromosome.

mutantbase

: the mutant base in the chromosome.

min

: a number min or more consecutive mutations.

max

: a distance less than or equal to a number max of bp.

Author

David Lora

Details

By default, features() identifies the mutations in the hyper-mutated zones (min = 6; max=5000). Complex mutations (Roberts et al. 2012; Roberts et al. 2013) are those segments containing >= 2 consecutive mutations with a distance =< 100 bp.

References

Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013 Aug 22;500(7463):415-21.

Nik-Zainal S, Alexandrov LB, Wedge DC, et al; Breast Cancer Working Group of the International Cancer Genome Consortium. Mutational processes molding the genomes of 21 breast cancers. Cell. 2012 May 25;149(5):979-93.

Roberts SA, Sterling J, Thompson C, et al. Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol Cell. 2012 May 25;46(4):424-35.

Roberts SA, Lawrence MS, Klimczak LJ, et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet. 2013 Sep;45(9):970-6.

Examples

data(PD4107a)
###Show the features of mutations in the hypermutated zones;
features(data=PD4107a,chr=Chr,position=Position,refbase=Ref_base,
		mutantbase=Mutant_base)

###Locate complex mutations in the hypermutated zones;
kataegis<-features(data=PD4107a,chr=Chr,position=Position,refbase=Ref_base,
		mutantbase=Mutant_base)
complex <-features(data=PD4107a,chr=Chr,position=Position,
			refbase=Ref_base,mutantbase=Mutant_base,min=2,max=10)
sub.complex <-subset(complex,select=c(clustered,chr,position))
data.hyperm  <-merge(kataegis,sub.complex,by=c("chr","position"),all.x=TRUE) 

###Summary of the number of complex mutations in the hypermutated zones;
table(data.hyperm$clustered.x)
table(data.hyperm$clustered.y)
table(data.hyperm$clustered.y,data.hyperm$clustered.x)
data.hyperm<-transform(data.hyperm,clustered = 
				ifelse(is.na(clustered.y)==FALSE,1,0))
table(data.hyperm$clustered.x)
table(data.hyperm$clustered,data.hyperm$clustered.x)
###All hypermutated zones had more than 6 mutations (without complex mutations).