buildPhylipLineage - Infer an Ig lineage using PHYLIP
buildPhylipLineage reconstructs an Ig lineage via maximum parsimony using the
dnapars application, or maximum liklihood using the dnaml application of the PHYLIP package.
buildPhylipLineage( clone, phylip_exec, dist_mat = getDNAMatrix(gap = 0), rm_temp = FALSE, verbose = FALSE, phylo = FALSE, temp_path = NULL )
- ChangeoClone object containing clone data.
- absolute path to the PHYLIP dnapars executable.
- Character distance matrix to use for reassigning edge weights.
Defaults to a Hamming distance matrix returned by getDNAMatrix
gap=0. If gap characters,
c("-", "."), are assigned a value of -1 in
dist_matthen contiguous gaps of any run length, which are not present in both sequences, will be counted as a distance of 1. Meaning, indels of any length will increase the sequence distance by 1. Gap values other than -1 will return a distance that does not consider indels as a special case.
TRUEdelete the temporary directory after running dnapars; if
FALSEkeep the temporary directory.
FALSEsuppress the output of dnapars; if
TRUESTDOUT and STDERR of dnapars will be passed to the console.
- return tree as a
- specific path to temp directory if desired
graph object defining the Ig lineage tree. Each unique input
clone is a vertex of the tree, with additional vertices being
either the germline (root) sequences or inferred intermediates. The
object has the following attributes.
name: value in the
sequence_idcolumn of the
dataslot of the input
clonefor observed sequences. The germline (root) vertex is assigned the name “Germline” and inferred intermediates are assigned names with the format “Inferred1”, “Inferred2”, ....
sequence: value in the
sequencecolumn of the
dataslot of the input
clonefor observed sequences. The germline (root) vertex is assigned the sequence in the
germlineslot of the input
clone. The sequence of inferred intermediates are extracted from the dnapars output.
label: same as the
Additionally, each other column in the
data slot of the input
clone is added as a vertex attribute with the attribute name set to
the source column name. For the germline and inferred intermediate vertices,
these additional vertex attributes are all assigned a value of
weight: Hamming distance between the
sequenceattributes of the two vertices.
label: same as the
clone: clone identifier from the
cloneslot of the input
v_gene: V-segment gene call from the
v_geneslot of the input
j_gene: J-segment gene call from the
j_geneslot of the input
junc_len: junction length (nucleotide count) from the
junc_lenslot of the input
Alternatively, this function will return an
phylo object, which is compatible
with the ape package. This object will contain reconstructed ancestral sequences in
buildPhylipLineage builds the lineage tree of a set of unique Ig sequences via
maximum parsimony through an external call to the dnapars application of the PHYLIP
package. dnapars is called with default algorithm options, except for the search option,
which is set to “Rearrange on one best tree”. The germline sequence of the clone is used
for the outgroup.
Following tree construction using dnapars, the dnapars output is modified to allow
input sequences to appear as internal nodes of the tree. Intermediate sequences
inferred by dnapars are replaced by children within the tree having a Hamming distance
of zero from their parent node. With the default
dist_mat, the distance calculation
allows IUPAC ambiguous character matches, where an ambiguous character has distance zero
to any character in the set of characters it represents. Distance calculation and movement of
child nodes up the tree is repeated until all parent-child pairs have a distance greater than zero
between them. The germline sequence (outgroup) is moved to the root of the tree and
excluded from the node replacement processes, which permits the trunk of the tree to be
the only edge with a distance of zero. Edge weights of the resultant tree are assigned
as the distance between each sequence.
- Felsenstein J. PHYLIP - Phylogeny Inference Package (Version 3.2). Cladistics. 1989 5:164-166.
- Stern JNH, Yaari G, Vander Heiden JA, et al. B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Sci Transl Med. 2014 6(248):248ra107.
### Not run: # Preprocess clone # db <- subset(ExampleDb, clone_id == 3138) # clone <- makeChangeoClone(db, text_fields=c("sample_id", "c_call"), # num_fields="duplicate_count") # # # Run PHYLIP and process output # phylip_exec <- "~/apps/phylip-3.695/bin/dnapars" # graph <- buildPhylipLineage(clone, phylip_exec, rm_temp=TRUE) # # # Plot graph with a tree layout # library(igraph) # plot(graph, layout=layout_as_tree, vertex.label=V(graph)$c_call, # vertex.size=50, edge.arrow.mode=0, vertex.color="grey80") # # # To consider each indel event as a mutation, change the masking character # # and distance matrix # clone <- makeChangeoClone(db, text_fields=c("sample_id", "c_call"), # num_fields="duplicate_count", mask_char="-") # graph <- buildPhylipLineage(clone, phylip_exec, dist_mat=getDNAMatrix(gap=-1), # rm_temp=TRUE)