Introduction
microRNAs (miRNAs) and microRNA-independent RNA-binding proteins (RBPs) are two classes of
post-transcriptional
regulators that have been shown to cooperate in gene-expression regulation.
simiRa compares target genes and enriched functional categories (pathways and GO
terms) of miRNAs and RBPs. It helps to identify microRNAs and RBPs
with a similar functional context and find potential interaction partners by exploring the
functional neighborhood of a miRNA/RBP.
Data
simiRa uses data generated by CLIP methods and does not rely on target prediction.
miRNA targets are provided by starBase v2.0, a database that collects and integrates
CLIP-Seq
experiments (http://starbase.sysu.edu.cn/). We downloaded the complete set of human miRNA target
sites with the minimal requirement
of one supporting experiment. The dataset contains 366 miRNAs with 536888 miRNA-mRNA interactions
(i.e. binding sites). RBP binding sites were extracted from the doRiNA database.
Similarity
simiRa calculates the similarity of target genes and enriched functional categories for a pair of
miRNAs or
RBPs with the Jaccard index (intersection divided by union).
The Jaccard index is in the interval [0,1], where 0 indicates no overlap between the compared
elements and 1 indicates that both have the same
targets/categories.
simiRa uses a Jaccard index threshold of 0.2 for category similarity and 0.3 for gene similarity to
show the top ranking results. In general, the
Jaccard index for gene similarities is higher than for categories.
Search
Start by searching for an miRNA or RBP in the search field in the 'Find miRNA/RBP' panel
on the left. The 'Show full list' button opens a list of all miRNAs and RBPs. A fuzzy search is
carried out upon typing of a miRNA/RBP name and results are shown in the 'Select' panel in the
center. Clicking on a miRNA/RBP loads the network view of similar miRNAs/RBPs. Settings can be
adjusted in the 'Search settings' panel on the right.
Result
The resulting similar miRNAs/RBPs are displayed in a network visualization in the 'miRNA-RBP
similarity network' panel. Similarity in gene targets is indicated by green edges, common enriched
categories are denoted by red edges. The user can zoom by scrolling and pan by dragging. Targets and
enriched categories of selected nodes are shown below the network panel. The network can be extended
by selecting a node and clicking 'Expand selection'. This allows for the stepwise exploration of the
functional neighborhood of a miRNA/RBP of interest.
Working with the result network
Zoom by scrolling, pan the network by dragging.
Select an element in the network and click 'Expand' to show its neighbors.
Select multiple elements (Shift + left click) to show their targets/associated categories below the
network view.
Use the 'Layout' button to re-render the network layout and the 'Center' button to show the whole network.
Interpretation of the result
We developed simiRa to be a hypothesis generator for wet lab researchers working with miRNAs or RBPs
in the biological system of their interest. The starting point for the analysis should be a miRNA or RBP of
interested in the users' biological system. simiRa now searches for functionally similar miRNAs/RBPs,
which might be interesting candidates e.g. for co-over-expression experiments.
