Category Cross-Omics>Knowledge Bases/Databases/Tools

Abstract miRò (The miR-Ontology Database) is a web-based knowledge base (KB) that provides users with miRNA-phenotype associations in humans.

It integrates data from various online sources, such as databases of miRNAs, ontologies, diseases and targets, into a unified database equipped with an intuitive and flexible query interface and data mining facilities.

The main goal of miRò is the establishment of a knowledge base (KB) which allows non-trivial analysis through sophisticated mining techniques and the introduction of a new layer of associations between genes and phenotypes inferred based on miRNAs annotations.

Furthermore, a specificity function applied to validated data highlights the most significant associations.

miRò Data Integration --

The miRò web site integrates data from different sources. miRNAs are annotated with information about their precursor and mature sequences coming from miRBase, and with expression profiles obtained from the Mammalian microRNA Atlas.

The miRNA Atlas contains expression patterns of pre-miRNAs and mature miRNAs in several kinds of tissues, both normal and malignant.

miRNAs are also associated with GO terms and diseases through their targets: each miRNA inherits all the annotations of its target genes. Experimentally supported miRNA/target pairs come from miRecords.

The predicted targets are taken from the web sites of TargetScan, PicTar, and miRanda.

The target genes records are enriched with general information such as genomic context and transcript-related data that comes from the NCBI Gene and Nucleotide Databases.

The ontological terms with which the target genes are annotated (processes and functions) are obtained from the Gene Ontology (GO) Database.

Finally, the gene-disease relations come from the Genetic Association Database (GAD); which is a database of human genetic association studies of complex diseases and disorders.

All the data is collected and maintained up-to-date in a MySQL database.

In particular, the most relevant data about the miRNAs and the target genes, such as the genomic contexts and the sequences, are stored in the database for an immediate availability, while links to the original sources are provided for more detailed information.

The miRò web interface --

The miRò web interface allows the user to perform four (4) different types of queries. A simple search is used to get information about a single object, which can be a miRNA, a gene, a process, a function, a disease or a tissue.

For example, it is possible to specify a miRNA or to choose one from the complete miRNA catalog to get the list of all the diseases and GO Terms (Processes and functions) which can be associated to that miRNA through its targets.

The results are ordered by the number of tools which predict the corresponding miRNA-target pairs and the experimentally supported associations are always given first.

Using the ‘AND’ constraint enables users to select only the terms associated to the targets predicted by all the selected tools. This may help to identify the most strongly supported associations, and reduce falsely predicted associations.

Similarly, the user can search for all the miRNAs associated with a certain gene, disease, process or function and obtain a list of all the miRNAs expressed in a certain tissue with their expression levels.

A customized search also allows users to extend the knowledge base by a personal set of miRNA-target pairs. These pairs will be temporarily stored and used in all the session queries. This feature may be helpful in testing new miRNA-target data.

The advanced search form can be used to perform more sophisticated queries. The user chooses a ‘subject’ among miRNA, gene, disease, process, and function, then specifies a list of constraints that the subject must satisfy.

For example, it is to possible to ask miRò to show all the miRNAs (the subject is ‘miRNA’) which are associated to ‘heart failure’, ‘RNA binding’ and ‘apoptosis’, but Not to ‘congenital heart diseases’.

The user may also choose the sources of the miRNA-target pairs. This allows you to tighten or relax the query conditions, in order to get a smaller or a larger output, respectively.

The system will show a list of all the miRNAs which satisfy these constraints, with details about the involved targets. This query tool links objects through miRNA-based associations.

miRò Data mining --

Maximal frequent item sets of miRNAs -

Since miRNAs are associated with GO terms and diseases, they can be clustered according to their common terms, i.e. miRNAs which are associated with the same set of terms are grouped together.

miRò is equipped with a data mining module, based on a maximal frequent item set computation, which allows users to query the database and extract non-trivial subsets of miRNAs sharing some features.

The analysis is performed using different support thresholds: a high threshold allows you to obtain a small number of miRNA subsets associated with a great number of terms, while a low threshold gives more subsets associated with fewer terms.

Note: All the subsets have been pre-computed off-line on the dataset of the validated miRNA-target pairs.

In the miRò interface, the user may choose up to n miRNAs, together with association criteria (i.e. process or disease). The system will find all the subsets of the selected miRNAs and the processes or diseases which they are most closely associated to.

This may suggest that a set of miRNAs are acting cooperatively to carry out certain biological functions. Moreover, miRNA-term associations are scored in order to highlight the most significant ones.

miRò Use cases and validation --

The system has been tested on various known cases that come from the literature. miRò has been able to identify miRNA-disease and miRNA-process associations previously reported.

For additional info on miRò, see the following paper:

A. Laganà, S. Forte, A. Giudice, M. R. Arena, P. L. Puglisi, R. Giugno, A. Pulvirenti, D. Shasha, A. Ferro.; miRò: a miRNA knowledge base; Database 2009; Vol. 2009, bap008.

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G6G Abstract Number 20744

G6G Manufacturer Number 104328