Description

This track displays the 3-way regulatory potential (RP) score computed from alignments of human (hg16, Jul. '03), mouse (mm3, Feb. '03) and rat (rn3, Jun. '03). A 2-way RP score, computed from alignments of human and mouse only is also available on this browser.

RP scores compare frequencies of short alignment patterns between known regulatory elements and neutral DNA. Preliminary results from a calibration study investigating sensitivity and specificity of 3-way RP scores on the hemoglobin beta gene cluster suggest the use of a threshold ~0.0006 for identifying new putative regulatory elements.

The default viewing range for this track is from 0.00 to 0.01 (score values below the 0.00 default indicate resemblance to alignment patterns typical of neutral DNA, while score values above the 0.01 default indicate very marked resemblance to alignment patterns typical of regulatory elements in the training set). The range of RP scores from 0.00 to 0.01 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 3-way alignment.

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 Markov models. Training the score entails selecting appropriate alphabet (alignment column symbols) and order (length of the patterns = order + 1) for the Markov models, and estimating their transition probabilities, based on alignment data from known regulatory elements and ancestral repeats. The 3-way RP score uses a 10-symbol alphabet and order 2.

In the track, score values are displayed using a system of overlapping windows of size 100 bp along aligned 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.

Mouse and rat sequence data were provided by the Mouse and Rat Sequencing Consortia. The alignment data were created in collaboration with the UCSC Genome Bioinformatics group.

References

Blanchette M, Kent WJ, Riemer C, Elnitski L, Smit AFA, Roskin KM, Baertsch R, Rosenbloom K, Clawson H, Green ED, Haussler D, Miller W. Aligning Multiple Genomic Sequences with the Threaded Blockset Aligner. Genome Res. 2004 Apr;14(4):708-15.

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.