R: Infer an Ig lineage using PHYLIP

buildPhylipLineage {alakazam} | R Documentation

## Infer an Ig lineage using PHYLIP

### Description

`buildPhylipLineage` reconstructs an Ig lineage via maximum parsimony using the dnapars application of the PHYLIP package.

### Usage

    buildPhylipLineage(clone, dnapars_exec, dist_mat = getDNAMatrix(gap = 0),
      rm_temp = FALSE, verbose = FALSE)

### Arguments

`clone` | ChangeoClone object containing clone data.
`dnapars_exec` | absolute path to the PHYLIP dnapars executable.
`dist_mat` | Character distance matrix to use for reassigning edge weights. Defaults to a Hamming distance matrix returned by getDNAMatrix with `gap=0`. If gap characters, `c("-", ".")`, are assigned a value of -1 in `dist_mat` then 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.
`rm_temp` | if `TRUE` delete the temporary directory after running dnapars; if `FALSE` keep the temporary directory.
`verbose` | if `FALSE` suppress the output of dnapars; if `TRUE` STDOUT and STDERR of dnapars will be passed to the console.

### Details

`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.

### Value

An igraph `graph` object defining the Ig lineage tree. Each unique input sequence in `clone` is a vertex of the tree, with additional vertices being either the germline (root) sequences or inferred intermediates. The `graph` object has the following attributes.

Vertex attributes:

- `name`: value in the `SEQUENCE_ID` column of the `data` slot of the input `clone` for 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 `SEQUENCE` column of the `data` slot of the input `clone` for observed sequences. The germline (root) vertex is assigned the sequence in the `germline` slot of the input `clone`. The sequence of inferred intermediates are extracted from the dnapars output.

- `label`: same as the `name` attribute.

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 `NA`.

Edge attributes:

- `weight`: Hamming distance between the `sequence` attributes of the two vertices.

- `label`: same as the `weight` attribute.

Graph attributes:

- `clone`: clone identifier from the `clone` slot of the input `ChangeoClone`.

- `v_gene`: V-segment gene call from the `v_gene` slot of the input `ChangeoClone`.

- `j_gene`: J-segment gene call from the `j_gene` slot of the input `ChangeoClone`.

- `junc_len`: junction length (nucleotide count) from the `junc_len` slot of the input `ChangeoClone`.

### References

1. Felsenstein J. PHYLIP - Phylogeny Inference Package (Version 3.2). Cladistics. 1989 5:164-166.

2. 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.

### See Also

Takes as input a ChangeoClone. Temporary directories are created with makeTempDir. Distance is calculated using seqDist. See igraph and igraph.plotting for working with igraph `graph` objects.

### Examples

    ## Not run:
    # Preprocess clone
    db <- subset(ExampleDb, CLONE == 3138)
    clone <- makeChangeoClone(db, text_fields=c("SAMPLE", "ISOTYPE"),
                              num_fields="DUPCOUNT")

    # Run PHYLIP and process output
    dnapars_exec <- "~/apps/phylip-3.69/dnapars"
    graph <- buildPhylipLineage(clone, dnapars_exec, rm_temp=TRUE)

    # Plot graph with a tree layout
    library(igraph)
    plot(graph, layout=layout_as_tree, vertex.label=V(graph)$ISOTYPE,
         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", "ISOTYPE"),
                              num_fields="DUPCOUNT", mask_char="-")
    graph <- buildPhylipLineage(clone, dnapars_exec, dist_mat=getDNAMatrix(gap=-1),
                                rm_temp=TRUE)

    ## End(Not run)

[Package alakazam version 0.3.0 Index]