SynMiRapy

A database for cooperative microRNA therapy in metastatic melanoma

Introduction

The page shows cooperative miRNA pairs that are predicted for protein-coding genes of a regulatory network underlying metastatic melanoma. One can filter the table using the slider, selecting gene types of interest, or using the interactive scatter plot.

Interactive Plot

Brush or click the data points to filter the whole table. The raw dataset contains infinite values for logarithmic fold-change of miRNAs (Inf: the miRNA is not expressed in melanocytes; -Inf: the miRNA is not expressed in melanoma cells). For visualizing those miRNAs properly, we have replaced the infinite values with 10 and -10, respectively.

We combine gene types and miRNA expression profiles to predict whether or not a protein-coding gene is a potential therapeutic target. Specifically, for a tumor suppressor gene, we assume that upregulating its expression level will benefit patients. We predict it as a target when its targeting miRNAs are simultaneously upregulated or differentially regulated (one downregulated and the other upregulated). This allows efficient upregulation of the tumor suppressor gene by modulating the expression of its cooperative targeting miRNAs individually or jointly. For an oncogene, we assume that downregulating its expression level will benefit patients. So, we predict it as a target when its targeting miRNAs are simultaneously downregulated or differentially regulated. For an unclassified gene, we predict it as a target when its targeting miRNAs are simultaneously downregulated or upregulated.

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References

Xin Lai, Martin Eberhardt, Ulf Schmitz, Julio Vera. Systems biology-based investigation of cooperating microRNAs as monotherapy or adjuvant therapy in cancer. In press in Nucleic Acids Research 2019. doi 10.1093/nar/gkz638

Download Supplementary Tables S2, S3, and S4

Table legend

Triplex_name: name of triplexes (Gene-miR1-miR2); Triplex_MFE: minimum free energy of triplexes; Triplex_Con: equilibrium concentration of tripleesx; Triplex_score: score of triplexes; HGNC_symbol: HUGO gene symbol; Gene_type: type of genes; NRvsCR_log2FC: fold-change of protein-coding gene expression in log2 scale (non-responder vs complete responder); NRvsCR_pvalue: p-value of the differential gene expression analysis; miR1/2: name of cooperating miRNA; miR1/2_log2FC: fold-change of miRNA in log2 scale (melanoma cells vs melanocytes); Predictive_target: if the gene is predicted as a potential therapeutic target.