minNumMutationsTune - Parameter tuning for minNumMutations

Description

minNumMutationsTune helps with picking a threshold value for minNumMutations in createSubstitutionMatrix by tabulating the number of 5-mers for which substitution rates would be computed directly or inferred at various threshold values.

Usage

minNumMutationsTune(subCount, minNumMutationsRange)

Arguments

subCount
data.frame returned by createSubstitutionMatrix with numMutationsOnly=TRUE.
minNumMutationsRange
a number or a vector indicating the value or range of values of minNumMutations to try.

Value

A 3xn matrix, where n is the number of trial values of minNumMutations supplied in minNumMutationsRange. Each column corresponds to a value in minNumMutationsRange. The rows correspond to the number of 5-mers for which substitution rates would be computed directly using the 5-mer itself ("5mer"), using its inner 3-mer ("3mer"), and using the central 1-mer ("1mer"), respectively.

Details

At a given threshold value of minNumMutations, for a given 5-mer, if the total number of mutations is greater than the threshold and there are mutations to every other base, substitution rates are computed directly for the 5-mer using its mutations. Otherwise, mutations from 5-mers with the same inner 3-mer as the 5-mer of interest are aggregated. If the number of such mutations is greater than the threshold and there are mutations to every other base, these mutations are used for inferring the substitution rates for the 5-mer of interest; if not, mutations from all 5-mers with the same center nucleotide are aggregated and used for inferring the substitution rates for the 5-mer of interest (i.e. the 1-mer model).

References

  1. Yaari G, et al. Models of somatic hypermutation targeting and substitution based on synonymous mutations from high-throughput immunoglobulin sequencing data. Front Immunol. 2013 4(November):358.

Examples

# Subset example data to one isotype and sample as a demo
data(ExampleDb, package="alakazam")
db <- subset(ExampleDb, ISOTYPE == "IgA" & SAMPLE == "-1h")

# Count the number of mutations per 5-mer
subCount <- createSubstitutionMatrix(db, model="S", multipleMutation="independent",
returnModel="5mer", numMutationsOnly=TRUE)

# Tune minNumMutations
minNumMutationsTune(subCount, seq(from=10, to=100, by=10))
      10  20  30   40   50   60   70   80   90  100
5mer   5   2   1    1    0    0    0    0    0    0
3mer 143 111  53   22   17    2    1    1    1    0
1mer 876 911 970 1001 1007 1022 1023 1023 1023 1024

See also

See argument numMutationsOnly in createSubstitutionMatrix for generating the required input data.frame subCount. See argument minNumMutations in createSubstitutionMatrix for what it does.