Description

This track shows RNA secondary structure predictions made with the EvoFold program, a comparative method that exploits the evolutionary signal of genomic multiple-sequence alignments for identifying conserved functional RNA structures.

Display Conventions and Configuration

Track elements are labeled using the convention ID_strand_score. When zoomed out beyond the base level, secondary structure prediction regions are indicated by blocks, with the stem-pairing regions shown in a darker shade than unpaired regions. Arrows indicate the predicted strand. When zoomed in to the base level, the specific secondary structure predictions are shown in parenthesis format. The confidence score for each position is indicated in grayscale, with darker shades corresponding to higher scores.

The details page for each track element shows the predicted secondary structure (labeled SS anno), together with details of the multiple species alignments at that location. Substitutions relative to the Drosophila melanogaster sequence are color-coded according to their compatibility with the predicted secondary structure (see the color legend on the details page). Each prediction is assigned an overall score and a sequence of position-specific scores. The overall score measures evidence for any functional RNA structures in the given region, while the position-specific scores (0 - 9) measure the confidence of the base-specific annotations. Base-pairing positions are annotated with the same pair symbol. The offsets are provided to ease visual navigation of the alignment in terms of the D. melanogaster sequence. The offset is calculated (in units of ten) from the start position of the element on the positive strand or from the end position when on the negative strand.

The graphical display may be filtered to show only those track elements with scores that meet or exceed a certain threshhold. To set a threshhold, type the minimum score into the text box at the top of the description page.

Methods

Evofold makes use of phylogenetic stochastic context-free grammars (phylo-SCFGs), which are combined probabilistic models of RNA secondary structure and primary sequence evolution. The predictions consist of both a specific RNA secondary structure and an overall score. The overall score is essentially a log-odd score between a phylo-SCFG modeling the constrained evolution of stem-pairing regions and one which only models unpaired regions.

The predictions for this track were based on the conserved elements of a 12-way Drosophila alignment of the D. melanogaster (dm2), D. simulans (droSim1), D. sechellia (droSec1), D. yakuba (droYak2), D. erecta (droEre2), D. ananassae (droAna3), D. pseudoobscura (dp4), D. persimilis (droPer1), D. willistoni (droWil1), D. virilis (droVir3), D. mojavensis (droMoj3), and D. grimshawi (droGri2) assemblies. The 12-way Drosophila alignment was extracted from a 15-way insect alignment, which is the one displayed in the Conservation track.

Credits

The EvoFold program and browser track were developed by Jakob Skou Pedersen.

References

Prediction analysis

Stark A, Lin MF, Kheradpour P, Pedersen JS, Parts L, Carlson JW, Crosby MA, Rasmussen MD, Roy S, Deoras AN et al. Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures. Nature. 2007 Nov 8;450(7167):219-32. PMID: 17994088; PMC: PMC2474711

EvoFold

Pedersen JS, Bejerano G, Siepel A, Rosenbloom K, Lindblad-Toh K, Lander ES, Kent J, Miller W, Haussler D. Identification and classification of conserved RNA secondary structures in the human genome. PLoS Comput Biol. 2006 Apr;2(4):e33. PMID: 16628248; PMC: PMC1440920

Phylo-SCFGs

Knudsen B, Hein J. RNA secondary structure prediction using stochastic context-free grammars and evolutionary history. Bioinformatics. 1999 Jun;15(6):446-54. PMID: 10383470

Pedersen JS, Meyer IM, Forsberg R, Simmonds P, Hein J. A comparative method for finding and folding RNA secondary structures within protein-coding regions. Nucleic Acids Res. 2004;32(16):4925-36. PMID: 15448187; PMC: PMC519121

PhastCons

Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 2005 Aug;15(8):1034-50. PMID: 16024819; PMC: PMC1182216