For comparison we also ran the popular profile HMM software packages HMMer and SAM on the same training data sets, and computed transitive alignments exactly as described above.
In each case, the phylogeny resulting from our analysis of the concatenated amino acid alignments exactly matched established topology as described in the literature [ 12, 16, 28, 29].
Sequence alignment demonstrated that the full length SOCS6 transcript aligned exactly with the SOCS6 gene on the forward strand of chromosome 18.
For alignments to introns and intergenic regions we only accepted reads that aligned exactly once in the entire genome.
This means that we are not interested in alignments where the corresponding splicing sites (one from each sequence) do not align exactly.
These gene families were individually aligned and concatenated together to give an alignment of exactly 38,000 amino acids in length.
Interestingly, the alignment showed exactly the same sequence of VDRE in the promoter region of HLA-DRB1*0301 which has been shown to influence the expression of HLA allele DRB1*1501 recently by Ramagopalan et al [26] suggesting the bases for interaction of VDR with HLA-DRB1*0301.
The dependencies between these structures and the alignment are exactly the same as in the original problem formulation of Sankoff.
The trimmed alignment produced exactly the same topology as shown in Figure 4A, using both Maximum Likelihood (RaxML-BMGE-tree) and Bayesian (PhyloBayes-tree) approaches.
