createMutabilityMatrix - Builds a mutability model

Description

createMutabilityMatrix builds a 5-mer nucleotide mutability model by counting the number of mutations occuring in the center position for all 5-mer motifs.

Usage

createMutabilityMatrix(db, substitutionModel, model = c("RS", "S"),
sequenceColumn = "SEQUENCE_IMGT", germlineColumn = "GERMLINE_IMGT_D_MASK",
vCallColumn = "V_CALL", multipleMutation = c("independent", "ignore"),
minNumSeqMutations = 500, numSeqMutationsOnly = FALSE,
returnSource = FALSE)

Arguments

db
data.frame containing sequence data.
substitutionModel
matrix of 5-mer substitution rates built by createSubstitutionMatrix.
model
type of model to create. The default model, “RS”, creates a model by counting both replacement and silent mutations. The “S” specification builds a model by counting only silent mutations.
sequenceColumn
name of the column containing IMGT-gapped sample sequences.
germlineColumn
name of the column containing IMGT-gapped germline sequences.
vCallColumn
name of the column containing the V-segment allele call.
multipleMutation
string specifying how to handle multiple mutations occuring within the same 5-mer. If "independent" then multiple mutations within the same 5-mer are counted indepedently. If "ignore" then 5-mers with multiple mutations are excluded from the total mutation tally.
minNumSeqMutations
minimum number of mutations in sequences containing each 5-mer to compute the mutability rates. If the number is smaller than this threshold, the mutability for the 5-mer will be inferred. Default is 500. Not required if numSeqMutationsOnly=TRUE.
numSeqMutationsOnly
when TRUE, return only a vector counting the number of observed mutations in sequences containing each 5-mer. This option can be used for parameter tuning for minNumSeqMutations during preliminary analysis using minNumSeqMutationsTune. Default is FALSE.
returnSource
return the sources of 5-mer mutabilities (measured vs. inferred). Default is FALSE.

Value

When numSeqMutationsOnly is FALSE, a named numeric vector of 1024 normalized mutability rates for each 5-mer motif with names defining the 5-mer nucleotide sequence.

When numSeqMutationsOnly is TRUE, a named numeric vector of length 1024 counting the number of observed mutations in sequences containing each 5-mer.

Details

Caution: The targeting model functions do NOT support ambiguous characters in their inputs. You MUST make sure that your input and germline sequences do NOT contain ambiguous characters (especially if they are clonal consensuses returned from collapseClones).

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")

# Create model using only silent mutations
sub_model <- createSubstitutionMatrix(db, model="S")
mut_model <- createMutabilityMatrix(db, sub_model, model="S", 
minNumSeqMutations=200,
numSeqMutationsOnly=FALSE)

Warning:Insufficient number of mutations to infer some 5-mers. Filled with 0.


# Count the number of mutations in sequences containing each 5-mer
mut_count <- createMutabilityMatrix(db, sub_model, model="S", 
numSeqMutationsOnly=TRUE)

See also

extendMutabilityMatrix, createSubstitutionMatrix, createTargetingMatrix, createTargetingModel, minNumSeqMutationsTune