Description

This track displays regulatory potential (RP) scores computed from alignments of human, chimpanzee (panTro2), macaque (rheMac2), mouse (mm8), rat (rn4), dog (canFam2), and cow (bosTau2).

RP scores compare frequencies of short alignment patterns between known regulatory elements and neutral DNA. The sensitivity and specificity of RP scores were calibrated on the hemoglobin beta gene cluster. These results suggest a threshold of ~0.00 for the identification of new putative regulatory elements.

The default viewing range for this track is from 0.0 to 0.1. Score values below the 0.0 default lower limit indicate resemblance to alignment patterns typical of neutral DNA, while score values above the 0.1 default upper limit indicate very marked resemblance to alignment patterns typical of regulatory elements in the training set. The range of RP scores from 0.0 to 0.1 contains the prediction threshold suggested by calibration studies, and provides an effective visualization of the score for most genomic loci. However, the user can specify different viewing ranges if desired. Note: Absence of a score value at a given location indicates lack of sufficient alignment -- scores are computed for all regions of the reference genome in which no region of more than 100 bases lacks alignment in at least three non-human species.

This track may be configured in a variety of ways to highlight different aspects of the displayed information. Click the Graph configuration help link for an explanation of the configuration options.

Methods

The comparison employs log-ratios of transitions probabilities from two variable order Markov models. Training the score entails selecting appropriate alphabet (alignment column symbols) and maximal order (length of the longest patterns = order + 1) for the Markov models, and estimating their transition probabilities, based on alignment data from known regulatory elements and ancestral repeats. The scores in this track are computed using a maximal order of 2.

In the track, score values are displayed using a system of overlapping windows of size 100 bp along sufficiently alignable portions of the human sequence. Log-ratios are added over positions in a window, and the sum is normalized for length.

Credits

Work on RP scores is performed by members of the Comparative Genomics and Bioinformatics Center at Penn State University. More information on this research and the collection of known regulatory elements used in training the score can be found at this site.

References

King DC, Taylor J, Elnitski L, Chiaromonte F, Miller W, Hardison RC. Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences.. Genome Res. 2005 Aug;15(8):1051-60.

Kolbe D, Taylor J, Elnitski L, Eswara P, Li J, Miller W, Hardison RC, Chiaromonte F. Regulatory potential scores from genome-wide three-way alignments of human, mouse, and rat. Genome Res. 2004 Apr;14(4):700-7.