generateEvidence {tigger}

Generate evidence

Description

generateEvidence builds a table of evidence metrics for the final novel V allele detection and genotyping inferrences.

Usage

generateEvidence(
  data,
  novel,
  genotype,
  genotype_db,
  germline_db,
  j_call = "j_call",
  junction = "junction",
  fields = NULL
)

Arguments

data

a data.frame containing sequence data that has been passed through reassignAlleles to correct the allele assignments.

novel

the data.frame returned by findNovelAlleles.

genotype

the data.frame of alleles generated with inferGenotype denoting the genotype of the subject.

genotype_db

a vector of named nucleotide germline sequences in the genotype. Returned by genotypeFasta.

germline_db

the original uncorrected germline database used to by findNovelAlleles to identify novel alleles.

j_call

name of the column in data with J allele calls. Default is j_call.

junction

Junction region nucleotide sequence, which includes the CDR3 and the two flanking conserved codons. Default is junction.

fields

character vector of column names used to split the data to identify novel alleles, if any. If NULL then the data is not divided by grouping variables.

Value

Returns the genotype input data.frame with the following additional columns providing supporting evidence for each inferred allele:

• field_id: Data subset identifier, defined with the input paramter fields.

• A variable number of columns, specified with the input parameter fields.

• polymorphism_call: The novel allele call.

• novel_imgt: The novel allele sequence.

• closest_reference: The closest reference gene and allele in the germline_db database.

• closest_reference_imgt: Sequence of the closest reference gene and allele in the germline_db database.

• germline_call: The input (uncorrected) V call.

• germline_imgt: Germline sequence for germline_call.

• nt_diff: Number of nucleotides that differ between the new allele and the closest reference (closest_reference) in the germline_db database.

• nt_substitutions: A comma separated list of specific nucleotide differences (e.g. 112G>A) in the novel allele.

• aa_diff: Number of amino acids that differ between the new allele and the closest reference (closest_reference) in the germline_db database.

• aa_substitutions: A comma separated list with specific amino acid differences (e.g. 96A>N) in the novel allele.

• sequences: Number of sequences unambiguosly assigned to this allele.

• unmutated_sequences: Number of records with the unmutated novel allele sequence.

• unmutated_frequency: Proportion of records with the unmutated novel allele sequence (unmutated_sequences / sequences).

• allelic_percentage: Percentage at which the (unmutated) allele is observed in the sequence dataset compared to other (unmutated) alleles.

• unique_js: Number of unique J sequences found associated with the novel allele. The sequences are those who have been unambiguously assigned to the novel allelle (polymorphism_call).

• unique_cdr3s: Number of unique CDR3s associated with the inferred allele. The sequences are those who have been unambiguously assigned to the novel allelle (polymorphism_call).

• mut_min: Minimum mutation considered by the algorithm.

• mut_max: Maximum mutation considered by the algorithm.

• pos_min: First position of the sequence considered by the algorithm (IMGT numbering).

• pos_max: Last position of the sequence considered by the algorithm (IMGT numbering).

• y_intercept: The y-intercept above which positions were considered potentially polymorphic.

• alpha: Significance threshold to be used when constructing the confidence interval for the y-intercept.

• min_seqs: Input min_seqs. The minimum number of total sequences (within the desired mutational range and nucleotide range) required for the samples to be considered.

• j_max: Input j_max. The maximum fraction of sequences perfectly aligning to a potential novel allele that are allowed to utilize to a particular combination of junction length and J gene.

• min_frac: Input min_frac. The minimum fraction of sequences that must have usable nucleotides in a given position for that position to be considered.

• note: Comments regarding the novel allele inferrence.

See Also

See findNovelAlleles, inferGenotype and genotypeFasta for generating the required input.

Examples

# Generate input data
novel <- findNovelAlleles(AIRRDb, SampleGermlineIGHV,
    v_call="v_call", j_call="j_call", junction="junction", 
    junction_length="junction_length", seq="sequence_alignment")
genotype <- inferGenotype(AIRRDb, find_unmutated=TRUE, 
                          germline_db=SampleGermlineIGHV,
                          novel=novel,
                          v_call="v_call", seq="sequence_alignment")
genotype_db <- genotypeFasta(genotype, SampleGermlineIGHV, novel)
data_db <- reassignAlleles(AIRRDb, genotype_db, 
v_call="v_call", seq="sequence_alignment")

# Assemble evidence table
evidence <- generateEvidence(data_db, novel, genotype, 
                             genotype_db, SampleGermlineIGHV,
                             j_call = "j_call", 
                             junction = "junction")