miRNAVISA
Exploration of miRNA families
for hypotheses generation

 

The miRNAVISA users manual

Often computational miRNA research tools and databases find prominent use in downstream analysis by other computational pipelines rather than by biologists. miRNAVISA is a web application that allows interrogation and comparisons of miRNA families for hypotheses generation, and comparison of the per-species 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.

The results generated using miRNAVISA are useful say for understanding and contrasting closely related species in evolutionary terms, assessing the abundance and general properties of family-specific miRNA-directed regulation in these species, and evaluating common properties that may be shared amongst miRNA families. Biological investigations that are enabled by miRNAVISA may include, but are not limited to, the following.

The term miRNAVISA derives from a concatenation of miRNA and VISA. The term VISA connotes both the "visualizations" of data to allow easy correlation of analyzed variables (species, chromosomes, miRNA families) and "entry" into the exciting miRNA world.

Getting Started

The website offers access to three tools that are listed in the main menu:

Figure 1: miRNAVISA (v1.0) web server interface.

Inter-species Comparisons

Under this menu, the user can select a combination of two or more species together with at-least two families. The user can also opt to use the automated selection buttons for the popular (in terms of miRNA gene numbers) species vis-a-vis the largest miRNA families in the latest release of the miRBase database i.e., the central repository for miRNA research.

In the example below, chicken (Gallus gallus) and mouse (Mus musculus) are selected with the combination of the miRNA families mir-515, mir- 548, mir-466 and mir-663. The user can select a species or miRNA family by clicking on the respective buttons with their names.

Figure 2: miRNAVISA Inter-species Comparisons form.

After submitting the query, the program generates graphical output in the Scalable Vector Graphic (SVG) format. Two buttons are provided for either download or display of the graph. By clicking on the "Download graph" button user can download a compressed SVG picture and by clicking on the "Display graph" the program opens a new window with the graph (see below) for perusal. The graph shows comparisons of miRNA gene distribution based on user input of miRNA families and species, relative to all other species in the miRBase database.

Figure 3a: Sample results given a miRNAVISA inter-species comparison query (four families).

The results in Figure 3a imply that

Figure 3b: Sample results given a miRNAVISA inter-species comparison query (23 families).

Intra-species comparisons

The Intra-species comparisons menu offers the same user interface as the inter-species comparison menu. However, the intra-species comparisons menu only allows the selection of one species and at-least two but no more than 50 miRNA families. The user can also opt to use the automated selection buttons for the human genome (default genome) to assess the distribution of miRNA genes belonging to the largest (top) miRNA families which are specific only to the selected genome.

The graphical output, a genome miRNA genes/family map, shows the chromosomal distribution (rows) and per-family distribution (columns). The miRNA genes that are not mapped to any chromosome are reported under a predefined label 'Chunks/NoMap'. Figure 4 illustrates the genomic distribution of family-annotated miRNA genes in the human genome.

Figure 4: Sample results given a miRNAVISA intra-species comparison query. Genomic distribution of family-annotated human miRNA genes in the 50 largest miRNA families.
There are 1600 registered human miRNA genes in miRBase R19. About 61.2% (367 plus 612 genes) are classified into different miRNA families. Figure 4 shows genome-wide distribution of miRNA genes in the 50 largest miRNA families. Moreover, it is apparent from the figure that: Several hypotheses can be formulated based on the results in Figure 3 and 4 as discussed in the manuscript.

Family Query

The Family Query menu allows a keyword search based on standard miRBase nomenclature for the names of miRNA, miRNA genes, and their families. The names/keywords are case insensitive and can include:

Figure 5: Sample results a given miRNAVISA keyword or family query.
An error message is returned for unsuccessful keyword queries. The output of a successful miRNA family query includes:

Table 5 gives an overview of a query report under a keyword search "mir-515". The top section of the table reports the statistics of the miRNA gene family name and accession numbers. The bottom section of the table gives the gene accession numbers, gene name, chromosome, strand, species name, associated function, associated diseases and terms, expression status (up/down) and the reference database from which additional information about the gene is given in detail.

The contents of the reported tables can be filtered by simply typing letters in the "Search" box say for a unique name of interest to the user. The contents of the table are adaptively adjusted with each input of consecutive letters. The contents of the reported columns can also be sorted (column-wise) by simply clicking on the column name. The user can also sort the results in a table using multiple columns by holding down the Shift key and clicking on the desired columns.

The first graph (picture bellow) shows distribution by species of the searched miRNA family.

Keyword "mir-515" query report generated by miRNAVISA showing a detailed summary of the miRNA genes constituting the miRNA family mir-515, their location in different genomes, expression trends, their associated diseases or biochemical pathways and links to different databases where reference to the experimental evidence is given.

Figure 6: Distribution of miRNA genes constituting the miRNA family "mir-515" in different species.

Figure 6 shows the distribution of miRNA genes with both known (mapped) and unknown (unmapped) chromosomal co-ordinates in each species. Figure 7 shows a comparison of the DNA strand preferences of mapped miRNA genes on the right panel. The number of miRNA genes that have been mapped on the positive (+1; FWD) strand and negative (-1; REV) strand are shown in red and blue bars, respectively. The number of unmapped miRNA genes in each species is reported on the left panel (green bars) in Figure 7.

Figure 7: Strand preferences miRNA genes constituting the "mir-515" miRNA gene family. The right panel shows the DNA strand preferences and number of mapped miRNA genes in different species. The left panel shows the number of miRNA family "mir-515" genes with unknown chromosomal co-ordinates in each species.

The blue bars in Figure 7 are explained in the manuscript along with the inference that the miRNA family mir-515 are preferentially transcribed from the +1 DNA strand. All the miRNA families mir-515 genes have only been reported in primate species (Figure 6).

The user can download all the results of a query for their own use. These results are packaged in one archive file. All the graphs are in the Scalable Vector Graphs (SVG) file format and the tables are "tab separated" files that can easily be imported into any spreadsheet programs.

Citation

Please cite:

Timothy Kevin Kuria Kamanu, Aleksandar Radovanovic, John A. C. Archer, Vladimir B. Bajic,
Exploration of miRNA families for hypotheses generation

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