microRNA.org: A resource for predicted microRNA targets and expression

About this document

MicroRNA.org is a web-accessible information resource produced and maintained at cBio, the Computational Biology Center at Memorial Sloan Kettering Cancer Center (MSKCC). This document describes technical details of parameters and algorithmic details used to produce the January 2008 data release.

Reference

microRNA target predictions: 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.
miRanda algorithm : Human MicroRNA targets. John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS., PLoS Biol. 2005 Jul;3(7):e264.

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Summary

The MicroRNA.org site is a comprehensive resource 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. MicroRNA 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:

• The set of genes that are potentially regulated by a particular microRNA.
• The implied cooperativity of multiple microRNAs on a particular mRNA.
• MicroRNA expression profiles in various mammalian tissues.

Data

MicroRNA sequences were collected from MirBase release 10.0. Mammalian 3'UTR sequences from the rat (rno4), mouse (mm7) and human (hg18) genomes were downloaded from the UCSC genome browser.

MicroRNA expression profiles were collected from a recently published comprehensive cloning and sequencing effort of 172 human, 64 mouse and 16 rat small RNA libraries extracted from major organs and cell types (Landgraf et al., Cell, 129, (2007), 1401-1414). Expression values represent the number of cloned mature microRNAs that were sequenced in each library and reported as clone counts. The counts are normalized by the total number of microRNAs that were cloned in each library.

Prediction parameters

Predictions were generated using the 2004 version of the miRanda algorithm (John et al., PLoS Biology, 2, (2004), e363) with the following command-line options:

Score cutoff S>= 140
Energy cutoff E<= -7.0
Gap opening: -9.0
Gap extension -4.0
5' scaling: 4

The miRNA:mRNA alignment scores are based on optimization of a sum of match values using a dynamic programming algorithm using the following single-position match values (base-pairing values):
A:U = 5
G:C = 5
G:U = 1
All other base pairs (mismatches) = -3

The match value s(i) is multiplied by a position specific weight w(i) before being evaluated in the alignment algorithm. The position specific weights reflect the non-homogeneous effect of different positions, such as the importance of the 'seed' or 'nucleus' generally defined as positions 2-8. Thus the total score S for a particular alignment is

S = SUM(over i) [ w(i) s(i) ]

where the sum is taken along the alignment trace (which may include bulges, i.e., unpaired nucleotides, in one of the sequences, evaluated as 'gaps').

Caveat:

These base-pairing scores were optimized against a limited set of validated targets. We are currently (early 2008) in the process of refining these values and will probably refine the parameters by mid-2008. Therefore, target predictions may differ in subsequent releases. Users will have access to previous, archived releases through links on the site.

Conservation

We used PhastCons conservation score, which measures the evolutionary conservation of sequence blocks across multiple vertebrates using a phylogenetic hidden Markov model (Siepel et al., Genome research, 15, (2005), 1034-1050.), to filter out less conserved predicted target sites. Target sites are filtered for PhastCons 0.57, which roughly corresponds to conservation across all mammals.

Software and data files

The miRanda source code (labeled Jan 2008 version) is available on the microRNA.org web site under the LGPL open source license. Data files in tabular form (labeled Jan 2008) are also available for download.

Additional References

• First implementation of the miRanda dynamic programming algorithm and comprehensive application to the drosophila genome.
  microRNA Target Detection Enright AJ, John B, Gaul U, Tuschl T, Sander C and Marks DS Genome Biology (2003) 5;R1

• First comprehensive computational predicition of microRNA targets in the human genome and first publication of the hypothesis that a large fraction of human genes (more than 10%) may be regulated by microRNAs. Human MicroRNA Targets John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. PLoS Biology 2005 Jul;3(7):e264.

• Comprehensive cloning and sequencing effort of 172 human, 64 mouse and 16 rat small RNA libraries extracted from major organs and cell types. A mammalian microRNA expression atlas based on small RNA library sequencing. Landgraf P., et al., Cell2007 Jun 29;129(7):1401-14.