Table of Contents : In silico predictions :
Missense predictions | Splicing module | Micro-RNA predictions

Micro-RNA predictions

Alamut® Visual 2.1 introduced a new micro-RNA module. It enables the user to visualize 3'UTR variant impacts on micro-RNA (miRNA) target sites.

This module is available in the variant window when the variant is in the 3'UTR region.

Background on the prediction method

This micro-RNA module relies on the public domain part of the miRanda algorithm (see microRNA.org).
This algorithm detects potential microRNA target sites in genomic sequences. A dynamic programming local alignment is carried out between the query miRNA sequence (collected from the miRBase web site) and the genomic sequence. This alignment procedure scores based on sequence complementarity and not on sequence identity (the G:U wobble base pair is also permitted, but generally scores less than the more optimal matches).

Alamut® Visual points out micro-RNA target site prediction differences between the wild-type and the mutated sequences.
The miRanda parameters are set as: miranda -sc 120 -noenergy.

Using the micro-RNA module

To launch the micro-RNA module, click on the 'MicroRNA Report' button from the variant window :

Variant Window

A micro-RNA report shows up after computation:

Variant Window

Explanation

All micro-RNA predicted targets are classified in 4 sections: Removed, Modified, Added and Unchanged
for which 6 features are computed: targets, position in 3'UTR, alignment length, alignment score, identity and similarity.

Sections:

Removed (wild-type): list of micro-RNA target sites predicted to be in the wild-type sequence but not in the mutated one.
Modified (wild-type ⇒ mutant): list of micro-RNA target sites predicted in both wild-type and mutated sequences with at least one modified feature (position, length, score, identity or similarity).
Added (mutant): list of micro-RNA target sites predicted to be in the mutated sequence but not in the wild-type one.
Unchanged (extract): list of micro-RNA target sites predicted to be unchanged by the variant.
This list is only an extract with micro-RNA target sites already listed in the Removed or Modified sections; it may be empty.
Each reference between removed or modified micro-RNA target site and unchanged ones is showed by an index in parenthesis.
In the example given above, for instance, the micro-RNA target site hsa-miR-195*⁽¹⁾ is predicted to be modified and another target site is predicted to be unchanged in another position.

An individual link to the miRBase description for each micro-RNA and a global link to the microRNA.org listing for all target micro-RNA are given.

Features:

Targets: one of the 4 target files from microRNA.org (August 2010 release);
best predictions come from the file with good mirSVR score and conserved miRNA (☆☆).
Position in 3'UTR: position of the predicted micro-RNA in the 3'UTR;
the position is given in the wild-type sequence whenever it is possible.
Alignment length: alignment length of the predicted micro-RNA.
Alignment score: alignment score of the predicted micro-RNA.
Identity: identity of the predicted micro-RNA.
Similarity: similarity of the predicted micro-RNA.

References

Enright, AJ., John, B., Gaul, U., Tuschl, T., Sander, C., Marks, DS. (2003). MicroRNA targets in Drosophila. Genome Biology. 5 : R1.

John, B., Enright, AJ., Aravin, A., Tuschl, T., Sander, C., Marks, DS. (2004). Human MicroRNA targets. PLoS Biol, 3 : e264.

Betel, D., Wilson, M., Gabow, A., Marks, DS., Sander, C. (2007). The microRNA.org resource: targets and expression. Nucleic Acids Res. 36 : D149-53.

Betel, D., Koppal, A., Agius, P., Sander, C., Leslie, C. (2010). Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biology 11 : R90