Circ2Disease is a database that intergrated a comprehensive collection of human circRNA and disease associations. All those associations were manually retriewed from public literature. We also predicted the corresponding miRNA sponges of those validated circRNAs and integrated RBP informaiton from CircInteratome database. Then experimentally verified miRNA-disease associations and miRNA targets were united from several public databases. All those data formed a large regulation network to provide more information for users.

Now the database can provide browsing, searching, network analysis and downloading functions. See below for more details.

The Browse page for general perusal of the database based on different hierarchical classification of circRNAs and diseases trees. Selecting particular nodes will display a corresponding result table.

The Search page allows users to input one or more circRNA name, disease name or other keyword to query related associations in Circ2Disease. In addition, users can specify the verified experimental methods to filter the result.

When users initiate a search request, a tips panel displaying the search details appears at the top of the results page. Circ2Disease results are organized in a data table, with a single association record on each line that contains circRNA name, diseas name, expression pattern and PubMed ID. Users can click on the "click here to download" to download the data table and the "details" link to view detailed information of the particular association. All the detailed information are included in the download data table not only the gereral information.

Users can obtain detailed information in Circ2Disease by clicking on the "details" of the data table, which will open a page containing comprehensive information of the single record and provides links to external web sites, such as circBase and Genome Browser.Provides genomic annotation of circRNAs with a genome browser integrated into the web interface.

Validated circRNA-disease interactions were retriwed from literature.If any circRNA-miRNA sponge, circRNA-RBP interactions, miRNA target, and upstream or downstream genes were also extracted to generate circRNA regulatory network. This network page can be found here: circRNA_network page. This network will display as below:

The network page supports the following functions:

• Search: circRNA, miRNA, disease and gene can be input to search the network and is case-insensitive. The matched node will turn yellow and display in the center of the page.
• Zoom: Scroll the mouse wheel to zoom in and out of the network.
• Display: Grab and drag nodes; tap a node or edge to select; tap blank to unselect.
• Hide/Show: The selected nodes and edges will be hidden or shown.
• Neighbor: Click the "Neighbor" button to select nodes and edges connected to the previously selected node.
• Export: Export the displayed network to JPG or PNG file. You can save it on your local computer.

MicroRNA Sponge Detection: Potential miRNA binding sites on circRNAs were identified by targetscan and miRanda. We seperately ran TargetScan with default parameters and miRanda with the "strict" parameter. To increase the specificity, 6mer matches were excluded from the TargetScan result. The intersection of the two results were considered as the predicted miRNA sponge.

To investigate the association between those miRNAs, their targets and diseases, we integrated several public databases, i.e. three experimentally validated miRNA databases (HMDD v2.0, dbDEMC 2.0 and OncomiRDB) and two experimentally validated miRNA-target databases (miRTarBase and miRecords). For data from miRTarBase, only strong experimental evidence of MTIs (miRNA–target interactions) were retained for further network analysis. All these interactions formed a comprehesive circRNA-miRNA-gene regulatory network, which will help users to elucidate the pathogenesis of diseases and offer beneficial evidence for diagnosis and therapy.

Users can download all data in Circ2Disease from "Download" page, including:

• The experimentally validated circRNA-disease association data.
• The manually curated circRNA regulatory network derived from literature.
• CircRNA name and alias.
• CircRNA related diseases from literature.
• All diseases association with circRNAs and miRNAs.
• Predicted RBP interacting with circRNA from CircInteractome database.
• The experimentally verified miRNA-disease association data integrated from HMDD, OncomiRDB and dbDEMC databases.
• The experimentally verified miRNA target data integrated from miRecords and miRTarBase databases.

The "Help" drop-down menu displays tutorial and information about how to use Circ2Disease, containing circRNA alias and disease names in orignal paper and normalized name.

Liu Pengyuan's Lab: http://bioinformatics.zju.edu.cn. For any questions or suggestions about our website, please contact us: dxyao1984@163.com, and pyliu@zju.edu.cn.