distToNearest - Distance to nearest neighbor

Description

Get non-zero distance of every sequence (as defined by sequenceColumn) to its nearest sequence sharing same V gene, J gene, and sequence length.

Usage

distToNearest(db, sequenceColumn = "JUNCTION", vCallColumn = "V_CALL",
jCallColumn = "J_CALL", model = c("ham", "aa", "hh_s1f", "hh_s5f",
"mk_rs1nf", "mk_rs5nf", "m1n_compat", "hs1f_compat"), normalize = c("len",
"none"), symmetry = c("avg", "min"), first = TRUE, nproc = 1,
fields = NULL, cross = NULL, mst = FALSE)

Arguments

db
data.frame containing sequence data.
sequenceColumn
name of the column containing nucleotide sequences to compare. Also used to determine sequence length for grouping.
vCallColumn
name of the column containing the V-segment allele calls.
jCallColumn
name of the column containing the J-segment allele calls.
model
underlying SHM model, which must be one of c("ham", "aa", "hh_s1f", "hh_s5f", "mk_rs1nf", "hs1f_compat", "m1n_compat"). See Details for further information.
normalize
method of normalization. The default is "len", which divides the distance by the length of the sequence group. If "none" then no normalization if performed.
symmetry
if model is hs5f, distance between seq1 and seq2 is either the average (avg) of seq1->seq2 and seq2->seq1 or the minimum (min).
first
if TRUE only the first call of the gene assignments is used. if FALSE the union of ambiguous gene assignments is used to group all sequences with any overlapping gene calls.
nproc
number of cores to distribute the function over.
fields
additional fields to use for grouping.
cross
columns for grouping to calculate distances across groups (self vs others).
mst
if TRUE, return comma-separated branch lengths from minimum spanning tree.

Value

Returns a modified db data.frame with nearest neighbor distances in the DIST_NEAREST column if crossGrups=NULL or in the CROSS_DIST_NEAREST column if crossGroups was specified.

Details

The distance to nearest neighbor can be used to estimate a threshold for assigning Ig sequences to clonal groups. A histogram of the resulting vector is often bimodal, with the ideal threshold being a value that separates the two modes.

The following distance measures are accepted by the model parameter.

  • "ham": Single nucleotide Hamming distance matrix from getDNAMatrix with gaps assigned zero distance.
  • "aa": Single amino acid Hamming distance matrix from getAAMatrix.
  • "hh_s1f": Human single nucleotide distance matrix derived from HH_S1F with calcTargetingDistance.
  • "hh_s5f": Human 5-mer nucleotide context distance matix derived from HH_S5F with calcTargetingDistance.
  • "mk_rs1nf": Mouse single nucleotide distance matrix derived from MK_RS1NF with calcTargetingDistance.
  • "mk_rs5nf": Mouse 5-mer nucleotide context distance matrix derived from MK_RS1NF with calcTargetingDistance.
  • "hs1f_compat": Backwards compatible human single nucleotide distance matrix used in SHazaM v0.1.4 and Change-O v0.3.3.
  • "m1n_compat": Backwards compatibley mouse single nucleotide distance matrix used in SHazaM v0.1.4 and Change-O v0.3.3.

Note on NAs: if, for a given combination of V gene, J gene, and sequence length, there is only 1 sequence (as defined by sequenceColumn), NA is returned instead of a distance (since it has no neighbor). If for a given combination there are multiple sequences but only 1 unique sequence, (in which case every sequence in this group is the de facto nearest neighbor to each other, thus giving rise to distances of 0), NAs are returned instead of zero-distances.

References

  1. Smith DS, et al. Di- and trinucleotide target preferences of somatic mutagenesis in normal and autoreactive B cells. J Immunol. 1996 156:2642-52.
  2. Glanville J, Kuo TC, von Budingen H-C, et al. Naive antibody gene-segment frequencies are heritable and unaltered by chronic lymphocyte ablation. Proc Natl Acad Sci USA. 2011 108(50):20066-71.
  3. Yaari G, et al. Models of somatic hypermutation targeting and substitution based on synonymous mutations from high-throughput immunoglobulin sequencing data. Front Immunol. 2013 4:358.

Examples

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

# Use genotyped V assignments, Hamming distance, and normalize by junction length
dist <- distToNearest(db, vCallColumn="V_CALL_GENOTYPED", model="ham", 
first=FALSE, normalize="len")

Calculating distance to nearest neighbor


# Plot histogram of non-NA distances
p1 <- ggplot(data=subset(dist, !is.na(DIST_NEAREST))) + 
theme_bw() + 
ggtitle("Distance to nearest: Hamming") + 
xlab("distance") +
geom_histogram(aes(x=DIST_NEAREST), binwidth=0.025, 
fill="steelblue", color="white")
plot(p1)

4


# Use human 5-mer model
dist <- distToNearest(db, vCallColumn="V_CALL_GENOTYPED", model="hh_s5f")
Calculating distance to nearest neighbor

See also

See calcTargetingDistance for generating nucleotide distance matrices from a TargetingModel object. See HH_S5F, HH_S1F, MK_RS1NF, getDNAMatrix, and getAAMatrix for individual model details.