A R-sig-phylo question yesterday read as follows (very slightly paraphrased):
“Given a large newick tree e.g. from the new open tree of life (304959 tips) 
I want to calculate a pairwise distance between a small subset of species. The 
tricks I've seen so far [Ed. ape::cophenetic, which computes a N
× N patristic distance for a tree with N tips] do not work on 
a tree of that size. I want to determine single species to single
species distances without having an algorithm attempt to calculate the
distance for all possible species (which is what ape is doing).  Is there a
package/trick to accomplish this?”
As a matter of fact,
this can be done in a reasonably efficient way using the phytools function
fastHeight, which computes the height above the root of the MRCA of
any pair of species. That is because, for two species i and j,
the patristic distane between them is simply the sum of the heights above the 
root for species i and j minus two times the height above the root
of the common ancestor of i & j.
To show that this works fairly well, let's try to write a little custom function,
fastDist, to compute this distance using the heights as mentioned:
library(phytools)
fastDist<-function(tree,sp1,sp2){
    fastHeight(tree,sp1,sp1)+fastHeight(tree,sp2,sp2)-
        2*fastHeight(tree,sp1,sp2)
}
Now, let's test it on a somewhat large tree:
## simulate tree at random
tree<-rtree(n=5000)
sp1<-sample(tree$tip.label)[1]
sp1
## [1] "t941"
sp2<-sample(tree$tip.label)[2]
sp2
## [1] "t2799"
## compute using cophenetic
system.time(d<-cophenetic(tree)[sp1,sp2])
##    user  system elapsed 
##    5.20    0.68    5.96
d
## [1] 11.34199
## compute using fastDist
system.time(d<-fastDist(tree,sp1,sp2))
##    user  system elapsed 
##    0.05    0.00    0.04
d
## [1] 11.34199
Having done that, let's go for broke with a tree of 304,959, just as described:
tree<-rtree(n=304959)
tree
## 
## Phylogenetic tree with 304959 tips and 304958 internal nodes.
## 
## Tip labels:
##  t51258, t83258, t60186, t263493, t117091, t210153, ...
## 
## Rooted; includes branch lengths.
sp1<-sample(tree$tip.label)[1]
sp1
## [1] "t51585"
sp2<-sample(tree$tip.label)[2]
sp2
## [1] "t244730"
## just to check that our MRCA is not the root
fastMRCA(tree,sp1,sp2)
## [1] 427604
## compute using fastDist
system.time(d<-fastDist(tree,sp1,sp2))
##    user  system elapsed 
##    4.80    1.34    6.21
d
## [1] 12.93951
Cool.
Just for the heck of it, I have also added this function to phytools & it is available from GitHub already.
 
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