CSmiRTar

Understanding the miRNA-target interactions is the crucial step to discern the roles of miRNAs in different biological processes. Many databases have been developed to provide miRNA targets information. For example, TarBase and miRTarBase collect manually curated miRNA targets with experimental evidence from the literature but they are far from complete. The other databases such as TargetScan, miRDB, microRNA.org, DIANA-microT, miRecords, MAGIA, mirDIP, miRSystem, miRGator and miRwalk collect computationally predicted miRNA targets generated from various algorithms. However, these databases usually return thousands of predicted targets of a query miRNA. Researchers have to put extra efforts to extract the interested miRNA targets from a large number of uninterested ones. Since miRNAs regulate their targets in specific tissues, cell types and disease status, it is advantageous to have a database which can return miRNA targets in a specific physiological condition.

CSmiRTar (Condition-Specific miRNA Targets) database collects computationally predicted targets of 2588 human miRNAs and 1945 mouse miRNAs from four existing databases (miRDB, TargetScan, microRNA.org and DIANA-microT). CSmiRTar implements (i) a database filter for users to search the miRNA targets supported by multiple databases, (ii) a tissue filter for users to search the miRNA targets expressed in a specific tissue, and (iii) a disease filter for users to search the miRNA targets related to a specific disease. Moreover, CSmiRTar allows users to search the common targets of a set of input miRNAs under a specific physiological condition and the common miRNAs of a set of input genes under a specific physiological condition.

Four data sources were used to construct CSmiRTar.

1. The computationally predicted and experimentally validated human and mouse miRNA targets were retrieved from four existing databases (TargetScan, miRDB, microRNA.org and DIANA-microT) and miRTarBase, respectively.
2. The tissues in which a human or a mouse gene is expressed are known from Expression Atlas.
3. The diseases to which a human gene is related are known from Disgenet.
4. The diseases to which a human miRNA is related are known from Phenomir.

The statistics of CSmiRTar could be found in the following Table.

	# of collected miRNA-target pairs	# of miRNAs which can be queried	# of genes which can be queried	# of collected tissues in which a gene may be expressed	# of collected diseases to which a gene may be related	# of collected diseases to which a miRNA may be related
Human	19,006,454	2588	21137	81	3696	81
Mouse	6,949,317	1945	21049	51	X	X

Search mode:
Users have four possible ways to search CSmiRTar.

1. Users can input a miRNA and search its targets which are (i) expressed in a specific tissue, (ii) related to a specific disease, and/or (iii) supported by multiple existing databases. After submission, users will see the search results sorted by the number of supported databases or the average normalized score (ANS).
   

   
   Figure 1
   Search the target genes of an input miRNA. (a) Search human miR-139-3p’s target genes which express in the brain tissue, are related to the brain neoplasms disease and supported by at least two existing databases. (b) CSmirTar returns 35 target genes sorted by average normalized score (ANS). (c) When clicking on the name in the column of “Target Gene”, it opens a webpage showing the basic information of this gene, the tissues in which this gene is expressed and the diseases to which this gene is related. (d) When clicking on the score in the column of “ANS”, it opens a webpage showing how the ANS is calculated. (e) When clicking on the icon in the column of “Validated?”, it links to miRTarBase to show the experimental evidence of the selected miRNA-target pair.
2. Users can input a set of miRNAs and search their common targets which are (i) expressed in a specific tissue, (ii) related to a specific disease, and/or (iii) supported by multiple existing databases. After submission, users will see the search results sorted by the number of supported databases or the mean average normalized score (MANS).
   
   Figure 2
   Search the common targets of a set of input miRNAs. (a) For a set of human miRNAs (miR-29a-3p, miR-125b-5p and miR-620), search their common target genes which express in the breast tissue, are related to the breast carcinoma disease and supported by at least two existing databases. (b) CSmirTar returns 117 common target genes sorted by mean average normalized score (MANS). (c) When clicking on the name in the column of “Common Target Gene”, it opens a webpage showing the basic information of this gene, the tissues in which this gene is expressed and the diseases to which this gene is related. (d) Orange bar means that the miRNA-target pair has been experimentally validated. When clicking on the orange bar, it links to miRTarBase to show the experimental evidence of the selected miRNA-target pair. (e) When clicking on the score in the column of “MANS”, it opens a webpage showing how the MANS is calculated.
3. Users can input a gene and search its miRNAs which are (i) related to a specific disease and/or (ii) supported by multiple existing databases. After submission, users will see the search results sorted by the number of supported databases or the average normalized score (ANS).
   
   Figure 3
   Search the miRNAs of an input gene. (a) For human gene ABL2, search its miRNAs which are related to Parkinson disease and supported by at least two existing databases. (b) CSmirTar returns 33 miRNAs sorted by average normalized score (ANS). (c) When clicking on the name in the column of “miRNA”, it opens a webpage showing the basic information of this miRNA, the tissues in which this miRNA is expressed and the diseases to which this miRNA is related. (d) When clicking on the score in the column of “ANS”, it opens a webpage showing how the ANS is calculated. (e) When clicking on the icon in the column of “Validated?”, it links to miRTarBase to show the experimental evidence of the selected miRNA-target pair.
4. Users can input a set of genes and search their common miRNAs which are (i) related to a specific disease and/or (ii) supported by multiple existing databases. After submission, users will see the search results sorted by the number of supported databases or the mean average normalized score (MANS).
   
   Figure 4
   Search the common miRNAs of a set of input genes. (a) For a set of human genes (KCNC3, RBBP4, ADCY1, ABL2, and TP53), search their common miRNAs which are related to the hematological disease and supported by at least two existing databases. (b) CSmirTar returns 17 common miRNAs sorted by mean average normalized score (MANS). (c) When clicking on the name in the column of “Common miRNA”, it opens a webpage showing the basic information of this miRNA, the tissues in which this miRNA is expressed and the diseases to which this miRNA is related. (d) Orange bar means that the miRNA-target pair has been experimentally validated. When clicking on the orange bar, it links to miRTarBase to show the experimental evidence of the selected miRNA-target pair. (e) When clicking on the score in the column of “MANS”, it opens a webpage showing how the MANS is calculated.

Browse Mode:
Users have two possible ways to browse CSmiRTar.

1. Users can click on a human/mouse miRNA name and get the miRNA’s targets retrieved from one or multiple existing databases.
   
   Figure 5
   Browse CSmiRTar by a miRNA name. (a) The browse page. (b) 2588 human miRNAs which can be browsed are shown. (c) By clicking on the number 410, it opens a webpage showing the 410 predicted target genes of hsa-let-7a-2-3p supported by at least 3 of the 4 databases. (d) By clicking on the icon in the rightmost column, it directs users to the search page.
2. Users can click on a human/mouse gene name and get the miRNAs, which regulate the gene, retrieved from one or multiple existing databases.
   
   Figure 6
   Browse CSmiRTar by a gene name. (a) The browse page. (b) 567 human genes whose first alphabet is “E” are shown. (c) By clicking on the number 130, it opens a webpage showing the 130 miRNAs predicted to regulate E2F1 supported by at least 3 of the 4 databases. (d) By clicking on the icon in the rightmost column, it directs users to the search page.