Phylogenetic placement of metagenomic reads using the minimum evolution principle

A central problem of computational metagenomics is determining the correct placement into an existing phylogenetic tree of individual reads (nucleotide sequences of varying lengths, ranging from hundreds to thousands of bases) obtained using next-generation sequencing of DNA samples from a mixture of known and unknown species. Correct placement allows us to easily identify or classify the sequences in the sample as to taxonomic position or function.

Here we propose a novel method (PhyClass), based on the Minimum Evolution (ME) phylogenetic inference criterion, for determining the appropriate phylogenetic position of each read. Without using heuristics, the new approach efficiently finds the optimal placement of the unknown read in a reference phylogenetic tree given a sequence alignment for the taxa in the tree. In short, the total resulting branch length for the tree is computed for every possible placement of the unknown read and the placement that gives the smallest value for this total is the best (optimal) choice. By taking advantage of computational efficiencies and mathematical formulations, we are able to find the true optimal ME placement for each read in the phylogenetic tree. Using computer simulations, we assessed the accuracy of the new approach for different read lengths over a variety of data sets and phylogenetic trees. We found the accuracy of the new method to be good and comparable to existing Maximum Likelihood (ML) approaches.

In particular, we found that the consensus assignments based on ME and ML approaches are more correct than either method individually. This is true even when the statistical support for read assignments was low, which is inevitable given that individual reads are often short and come from only one gene.