Dme-Hsa Disease Database (DHDD): Conserved Human Disease-Related miRNA and Their Targeting Genes in Drosophila melanogaster

Abstract

Abnormal expressions of microRNA (miRNA) can result in human diseases such as cancer and neurodegenerative diseases. MiRNA mainly exert their biological functions via repressing the expression of their target genes. Drosophila melanogaster (D. melanogaster) is an ideal model for studying the molecular mechanisms behind biological phenotypes, including human diseases. In this study, we collected human and D. melanogaster miRNA as well as known human disease-related genes. In total, we identified 136 human disease-related miRNA that are orthologous to 83 D. melanogaster miRNA by mapping "seed sequence", and 677 human disease-related genes that are orthologous to 734 D. melanogaster genes using the DRSC Integrative Ortholog Prediction Tool Furthermore, we revealed the target relationship between genes and miRNA using miRTarBase database and target prediction software, including miRanda and TargetScan. In addition, we visualized interaction networks and signalling pathways for these filtered miRNA and target genes. Finally, we compiled all the above data and information to generate a database designated DHDD This is the first comprehensive collection of human disease-related miRNA and their targeting genes conserved in a D. melanogaster database. The DHDD provides a resource for easily searching human disease-related miRNA and their disease-related target genes as well as their orthologs in D. melanogaster, and conveniently identifying the regulatory relationships among them in the form of a visual network.

Keywords: Drosophila melanogaster; database; disease; miRNA.

Figure 1

The analysis workflow of human disease-related miRNA and genes with orthologs in the fruit fly.

Figure 2

Statistical number of human disease-related genes and miRNA orthologs with the fly in different disease groups.

Figure 3

Example diagram of a network. Oval nodes represent genes, triangle nodes represent miRNA, squares nodes represent disease groups and pathways. Orthologous miRNA or genes are linked with a yellow line; miRNA are connected to genes by red lines with an arrow; genes are linked to pathways by gray lines.

Figure 4

Web user interface, (a) on the search page, after entering a keyword, the result will be displayed and the list of the results will be displayed below; (b) On the browse page, select one group to display, the result is similar as on the search page. Both on the search and browse page, each row of the list is composed of five columns, human miRNA, fly miRNA, human gene, fly gene, gene disease group, where the human miRNA is orthologous to the fly miRNA, the human gene is orthologous to the fly gene, and the miRNA target to gene in human and fly, respectively.