REDR (RNA Editing in Drug Resistance) is a data website accompanying our "The Genomic Landscape and Potential Regulation of RNA Editing in Drug Resistance" paper, which curated predicted drug reponse-related RNA editing events based on TCGA data or CCLE data.

RNA editing events could affect the response of cancer therapies, suggesting RNA editing as a predictive marker of therapy response. However, limited by the number of examined RNA editing sites, drugs, samples, or tissues, the published studies did not thoroughly dissect the RNA editing-mediated mechanisms in drug response. Thus, systematic analysis of A-to-I editing associated with drug response is urgent and necessary. We hope that this elaborate database could provide new therapeutic strategies for overcoming the drug resistance of cancer cells.

REDR database contains the detail information of identified drug reponse-related RNA editing events based on TCGA data or CCLE data. Each entry includes the information of gene, region, chromosome location, strand, number of used sensitive samples, number of used resistant samples, the difference in the mean value of the editing level in resistant samples relative to sensitive samples, the statistical significance based on the Wilcoxon rank-sum test, condition(cancer and drug), and resource(TCGA or CCLE). Collectively, REDR include 80,494 entries that include 56,132 unique editing sites for 18 drugs across six cancer types. Furthermore, through a multi-step screening process, we identified 234 RNA editing-dependent post-transcriptional regulation triplets (including 206 DESs, 167 miRNAs, and 139 genes) across different conditions. In addition, REDR provides an online genome browser to show the genome locations of DESs.

1.How to search for DESs by condition?

If you want to review differential editing site (DESs) in a particular condition, e.g. BLCA-Cisplatin, you can select BLCA and Cisplatin and press "Search" button (Fig. 1). The results list all potential entries related to your inputted BLCA-Cisplatin (Fig. 2). By clicking the button above the table, you can obtain the results based on TCGA or CCLE data. You can also view the DES in Genome Browser by clicking on "View".

Fig. 1. Search DESs by condition.

Fig. 2. The serach results of "BLCA-Cisplatin".

2.How to search for DESs by gene?

If you want to query a gene which harbored differential editing site (DESs) between resistant and sensitive group, e.g. TEP1, you can input TEP1 and press "Search" button (Fig. 3). The results list all potential entries related to your inputted TEP1. The basic information about the DESs in the gene is returned (Fig. 4). By clicking the button above the table, you can obtain the results based on TCGA or CCLE data.

Fig. 3. Search DESs by gene name.

Fig. 4. The serach results of "TEP1".

3.How to search for Triplets by miRNA?

If you want to query which miRNA regulation affected by DESs, you can select a miRNA, e.g. miR-484, you should select the miRNA name "miR-484" from the miRNA name pull-down menu (Fig. 5). The results list all potential entries related to your inputted "miR-484". The information of miRNA regulation affected by DESs about the miRNAs are returned (Fig. 6). Then click "View", you can get the more detailed information in miRNA regulation (Fig. 7). Here, "UTR start" and "UTR end" represent the location information of miRNA binding in a gene. The information of "bind type" from TargetScan. "seed m8" and "mature sequence" represent the seed region and mature sequence of the miRNA.

Fig. 5. Search triplets by miRNA.

Fig. 6. The search results of "miR-484".

Fig. 7. The detail information of the triplet, "chr11:36507636_miR-484_TRAF6".

4.How to search for Triplets by gene?

Similar to Search II, If you want to query which gene in miRNA regulation affected by DESs, you can select a gene, e.g. TRAF6, you should select the gene symbol TRAF6 from the gene symbol pull-down menu (Fig. 8). The results list all potential entries related to your inputted TRAF6. The information of miRNA regulation affected by DESs about the miRNAs are returned (Fig. 9). Then click "View", you can get the more detailed information in miRNA regulation (Fig. 10).

Fig. 8. Search triplets by gene.

Fig. 9. The search results of "miR-27a-3p".

Fig. 10. The detail information of the triplet, "chr5:132031002_miR-27a-3p_KIF3A".

Genome Browser

REDR uses the embedded JBrowse for visualization of the genome locations of the DESs in the track. Firstly, you can select chromosome number and input genome start site such as "20,836,038" and end site such as "20,836,054" in search box of genome browser (Fig. 11). Then press "Enter" button to search. You can click the right mouse button and open feature detail (Fig. 12) to review the detail information of the DES(Fig. 13). In addition, you can directly enter gene symbol into the search box to query information of interest, e.g. TEP1 (Fig. 14).

Fig. 11. Search DESs by chromosome in Gemome Browser.

Fig. 12. Open feature detail of the DESs in Gemome Browser.

Fig. 13. The detail information of chr14:20,836,040.

Fig. 14. Search DESs by gene in Gemome Browser.

Triplet

You can browse any Triplets, which you are interested in by browsing detail information of miRNA or gene. Then, click on the green button, e.g. "hsa-miR-9-5p"(Fig. 15) or "AAK1"(Fig. 16), and all entries related to your choose are returned (Fig. 17 or 18). Next, click "View", you can get the detailed information.

Fig. 15. Browse triplet by miRNAs.

Fig. 16. The Browse triplet by genes.

Fig. 17. The result of "hsa-miR-106a-3p".

Fig. 18. The result of "AAK1".

• A-to-I: Adenosine-to-inosine

• 3'UTR: 3'-untranslated region

• 5'UTR: 5'-untranslated region

• BLCA: Bladder urothelial carcinoma

• BRCA: Breast invasive carcinoma

• CCLE: Cancer Cell Line Encyclopedia

• CDS: the coding sequence

• chr: chromosome

• DES: Differential Editing Site

• expr.: expression

• GDSC: Genomics of Drug Sensitivity in Cancer

• HNSC: Head and Neck squamous cell carcinoma

• LGG: Brain lower grade glioma

• LUAD: Lung adenocarcinoma

• ncRNA: non-coding RNA

• res.: resisitant

• sen.: sensitive

• STAD: Stomach adenocarcinoma

• TCGA: The Cancer Genome Atlas

Wei Jiang, Professor

Department of Biomedical Engineering, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics

Email: weijiang@nuaa.edu.cn

Website: http://www.jianglab.cn/