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About

microRNA (miRNA) are a class of small endogenous non-coding RNA that are mainly negative transcriptional and post-transcriptional regulators in both plants and animals. Recent studies have shown that miRNA are involved in different types of cancer and other diseases such as autism and Alzheimer’s that are yet to be fully understood.

Functional ~22nt mature miRNAs are excised from longer hairpin-like sequences that are known as miRNA genes (see the illustrations below).

The central repository for miRNA research, miRBase (release 19, dated August 2012), contains 21,264 validated miRNA genes expressing 25,141 mature miRNA in 193 species. About 73% (15,554) of the miRNA genes at miRBase have been assigned into 1,543 miRNA families based on their sequence and structural properties.
miRNAVISA is a web-based tool that allows customized interrogation and comparisons of miRNA families for hypotheses generation, and comparison of the per-species chromosomal distribution of miRNA genes in different families.

Technological improvements have resulted in increased discovery of new microRNAs (miRNAs) and refinement and enrichment of existing miRNA families. Elucidating function of miRNAs and their influence on biochemical pathways and diseases is, however, challenging. miRNA families are important because they suggest a common sequence or structure configuration in sets of genes that hint to a shared function. However, exploratory tools to enhance investigation of the functions of family-specific miRNA genes are lacking.

We have developed, miRNAVISA, a user-friendly tool that allows customized interrogation and comparisons of miRNA families for hypotheses generation, inter-species comparisons, and intra-species comparison of the chromosomal distribution of miRNA genes in different families. The design and implementation of the miRNAVISA system is targeted for use by both the biological and computational scientists.

Biological investigations that are enabled by miRNAVISA may include, but are not limited to, the following.

• Enhancing a hypothesis-driven analysis of the properties of miRNA, miRNA gene and miRNA families.
• Investigating the chromosomal distribution of family-annotated miRNA and miRNA genes in different species e.g. for downstream examination and testing of miRNA regulation models (miRNA promoters).
• Evaluating the diversity of different miRNA families across species or a lineage.
• Summarizing the miRNA knowledge database (miRBase) given a set of specific species of interest.
• Jointly interrogating and integrating the genomic distribution of miRNA, miRNA gene organization (e.g. co-location on specific chromosomes), and sequence and/or structure organization of miRNA genes and the functions of their associated mature miRNA that may be encoded and implied by miRNA family categories.
• Evaluating specific attributes and characteristics, such as the chromosomal distribution of miRNA genes, that may define inter-miRNA family relationships and existence of miRNA subclasses comprising of different miRNA families [clan(s) of families].
• Examining and analyzing the (up/down) expression trends of the functional mature miRNA in a specific miRNA family, based on integrated experimental evidence contained in different public miRNA databases.
• Assessing the link of family-specific mature miRNA and their genes to different diseases and biochemical pathways.
• Assessing the yet-to-be-determined function of family-annotated miRNA genes given the known function(s) of miRNA and miRNA genes in the same family.
• Improving in vitro and in vivo experimental designs given the result summarized in miRNAVISA inter-species comparison and/or intra-species miRNA genes/family maps.
• Evaluating DNA strand preferences of miRNA genes in a specific miRNA family.

Our study demonstrates the generation of hypotheses using miRNAVISA in seven species. Our results unveil a subclass of miRNA that may be regulated by genomic imprinting. Further, the results suggest that miRNA families may not only be species-specific, but can also be chromosome- and/or strand-specific.

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