PhastCons Vert17, Genome Conservation Scores

Description

This track shows a measure of evolutionary conservation in 17 vertebrates, including mammalian, amphibian, bird, and fish species, based on a phylogenetic hidden Markov model, phastCons (Siepel et al., 2005). Multiz alignments of the following assemblies were used to generate this track:

Source

PhastCons scores were downloaded from the UCSC Genome Browser via URL: ftp://hgdownload.cse.ucsc.edu/goldenPath/hg18/phastCons17way

Samples

From Human Mar. 2006 (NCBI36/hg18) Assembly

Filename Description Feature GEO-ID
1 phastcons.sga PHASTCONS VERT17 PHASTCONS -

Technical Notes

Best-in-genome pairwise alignments were generated for each species using blastz, followed by chaining and netting. The pairwise alignments were then multiply aligned using multiz, following the ordering of the species tree diagrammed above. The resulting multiple alignments were then assigned conservation scores by phastCons, using a tree model with branch lengths derived from the ENCODE project Multi-Species Sequence Analysis group, September 2005 tree model. This tree was generated from TBA alignments over 23 vertebrate species and is based on 4D sites. The phastCons parameters were tuned to produce 5% conserved elements in the genome: expected-length=14, target-coverage=.008, rho=.28. The phastCons program computes conservation scores based on a phylo-HMM, a type of probabilistic model that describes both the process of DNA substitution at each site in a genome and the way this process changes from one site to the next (Felsenstein and Churchill 1996, Yang 1995, Siepel and Haussler 2005). PhastCons uses a two-state phylo-HMM, with a state for conserved regions and a state for non-conserved regions. The value plotted at each site is the posterior probability that the corresponding alignment column was "generated" by the conserved state of the phylo-HMM. These scores reflect the phylogeny (including branch lengths) of the species in question, a continuous-time Markov model of the nucleotide substitution process, and a tendency for conservation levels to be autocorrelated along the genome (i.e., to be similar at adjacent sites). The general reversible (REV) substitution model was used. Note that, unlike many conservation-scoring programs, phastCons does not rely on a sliding window of fixed size, so short highly-conserved regions and long moderately conserved regions can both obtain high scores. More information about phastCons can be found in Siepel et al. (2005). PhastCons currently treats alignment gaps as missing data, which sometimes has the effect of producing undesirably high conservation scores in gappy regions of the alignment. We are looking at several possible ways of improving the handling of alignment gaps.

References

  1. Siepel, A. and Haussler, D et al.
    Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034-1050 (2005). PMID: 16024819