microRNA.org website

Category Cross-Omics>Knowledge Bases/Databases/Tools

Abstract The microRNA.org website is a comprehensive resource (database) of microRNA target predictions and expression profiles.

Target predictions are based on a development of the miRanda algorithm which incorporates current biological knowledge on target rules and on the use of an up-to-date compendium of mammalian microRNAs (see below...).

The target sites predicted by miRanda are scored for likelihood of mRNA down-regulation using mirSVR, a regression model that is trained on sequence and contextual features of the predicted miRNA::mRNA duplex (see below...)

Expression profiles are derived from a comprehensive sequencing project of a large set of mammalian tissues and cell lines of normal and disease origin.

This website enables users to explore:

1) The set of genes that are potentially regulated by a particular microRNA.

2) The co-occurrence of predicted target sites for multiple microRNAs in an mRNA.

3) MicroRNA expression profiles in various mammalian tissues.

New version of miRanda target prediction algorithm --

Target predictions are performed using the miRanda algorithm that computes optimal sequence complementarity between a set of mature microRNAs and a given mRNA using a weighted dynamic programming algorithm.

For additional detail info on Target prediction(s), see the paper: The microRNA.org resource: targets and expression. Betel D, Wilson M, Gabow A, Marks DS, Sander C., Nucleic Acids Res. 2008 Jan; 36 (Database Issue): D149-53.

There have been several minor corrections and simplifications to the miRanda source code. Changes include:

1) Default command line arguments altered to -sc 140 -go -9 -ge -4 -en 1 (no energy filtering);

2) Limit on UTR length removed;

3) Overlap filtering of predicted target sites tightened; requires overlap in seed region to filter; and

4) Offsets corrected in “score for this scan” output lines and -keyval output.

Prediction of target sites by miRanda --

Because of the website interface’s more flexible filtering of predicted target sites, the manufacturers have used an alignment score threshold of 120 instead of the previous threshold of 140.

By default, the website interface will filter out many of these lower scoring sites, but you have several criteria which can be adjusted to allow you to view them.

Scoring of predicted target sites by mirSVR --

Details of the mirSVR scoring method can be found in the paper: Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Betel D, Koppal A, Agius P, Sander C, Leslie C., Genome Biology 2010 11:R90.

Briefly, mirSVR is a ‘regression model’ that computes a weighted sum of a number of sequence and context features of the predicted miRNA::mRNA duplex. The features are broadly divided into three (3) types:

1) Duplex features which includes base pairing at the seed region, and 3' end of the miRNA;

2) Sequence features which include A/U composition near the target sites and secondary structure accessibility; and

3) Global features such as length of the UTR, relative position of the target site in the UTR and conservation score.

mirSVR down-regulation scores are calibrated to correlate linearly with the extent of down-regulation and therefore enable accurate scoring of genes with multiple target sites by simple addition of the individual target scores.

Furthermore, the scores can be interpreted as an empirical probability of down-regulation, which provides a meaningful guide for selecting a score cutoff.

In addition, the composite approach of miRanda-generated alignments and mirSVR scores enables the judicious prediction of non-canonical sites (those with mismatch or GU wobble in the seed region) without inflating the number of false predictions.

The August 2010 release of microRNA.org includes all target site predictions which have either a 6-mer or better seed site, or a mirSVR score = -0.1.

MirSVR takes conservation into account when computing a score, so there is No longer any predefined cutoff for filtering target sites.

However, users are able to restrict the interface display using conservation as a criterion. The determination of conservation score for predicted target sites is now sensitive to sites which span intron junctions.

The August 2010 release of microRNA.org contains:

1) 16,228,619 predicted microRNA target sites in 34,911 distinct 3'UTR from isoforms of 19,898 human genes.

2) 7,459,149 predicted microRNA target sites in 28,287 distinct 3'UTR from isoforms of 19,231 mouse genes.

3) 586,068 predicted microRNA target sites in 6,865 distinct 3'UTR from isoforms of 6,256 rat genes.

4) 345,671 predicted microRNA target sites in 12,285 distinct 3'UTR from isoforms of 10,532 fruit-fly genes.

5) 230,901 predicted microRNA target sites in 12,228 distinct 3'UTR from isoforms of 10,124 nematode genes.

6) Target sites for 1,100 human microRNAs.

7) Target sites for 717 mouse microRNAs.

8) Target sites for 387 rat microRNAs.

9) Target sites for 186 fruit-fly microRNAs.

10) Target sites for 233 nematode microRNAs.

Note: The microRNA target predictions and expression data are available as tab delimited files. See the Downloads tab on the microRNA.org website.

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