minNumMutationsTune: Parameter tuning for minNumMutations

In shazam: Immunoglobulin Somatic Hypermutation Analysis

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.

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).

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.

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.

See Also

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

Examples

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

# Count the number of mutations per 5-mer
subCount <- createSubstitutionMatrix(db, sequenceColumn="sequence_alignment",
                                     germlineColumn="germline_alignment_d_mask",
                                     vCallColumn="v_call",
                                     model="s", multipleMutation="independent",
                                     returnModel="5mer", numMutationsOnly=TRUE)

# Tune minNumMutations
minNumMutationsTune(subCount, seq(from=10, to=80, by=10))
                                      

shazam documentation built on Oct. 3, 2023, 1:06 a.m.