MyomirDB: A unified database and server platform for muscle atrophy myomiRs, coregulatory networks and regulons

Abstract

Muscular atrophy or muscle loss is a multifactorial clinical condition during many critical illnesses like cancer, cardiovascular diseases, diabetes, pulmonary diseases etc. leading to fatigue and weakness and contributes towards a decreased quality of life. The proportion of older adults (>65 y) in the overall population is also growing and aging is another important factor causing muscle loss. Some muscle miRNAs (myomiRs) and their target genes have even been proposed as potential diagnostic, therapeutic and predictive markers for muscular atrophy. MyomirDB (http://www.myomirdb.in/) is a unique resource that provides a comprehensive, curated, user- friendly and detailed compilation of various miRNA bio-molecular interactions; miRNA-Transcription Factor-Target Gene co-regulatory networks and ~8000 tripartite regulons associated with 247 myomiRs which have been experimentally validated to be associated with various muscular atrophy conditions. For each database entry, MyomirDB compiles source organism, muscle atrophic condition, experiment duration, its level of expression, fold change, tissue of expression, experimental validation, disease and drug association, tissue-specific expression level, Gene Ontology and KEGG pathway associations. The web resource is a unique server platform which uses in-house scripts to construct miRNA-Transcription Factor-Target Gene co-regulatory networks and extract tri-partite regulons also called Feed Forward Loops. These unique features helps to offer mechanistic insights in disease pathology. Hence, MyomirDB is a unique platform for researchers working in this area to explore, fetch, compare and analyse atrophy associated miRNAs, their co-regulatory networks and FFL regulons.

Figure 1

The figure shows the screenshot of the ‘Browse’ option. This option allow the users to browse atrophy miRNAs using different query filters. There are five queries filters namely ‘Level of expression’, ‘Tissue of expression’, ‘Duration of experiment’, ‘Source Organism’.

Figure 2

The web images shows the ‘Browse by association’ option. User can search myomiRs based on (a) user defined gene list, (b) association as biomarker, (c) association with drug, (d) association with GO ID (e) association with GO term (f) association with KEGG ID (g) association with KEGG pathway name.

Figure 3

The screenshots of the information page of the myomirDB. (a) The web image of the information section of hsa-let-7b-5p. (b) The muscle atrophy association of the miRNA is compiled in a tabular format.

Figure 4

The web image of the third section of the miRNA information page. This section contains miRNA associated information i.e. drug association, expression level in different tissues and cell lines, association with different disease pathologies. The table can be searched through ‘Search’ box and information in table can be downloaded in Excel/PDF format.

Figure 5

The web images of the fourth section of the miRNA information page. (a) The section contains information on enriched GO of miRNA targets (b) The section lists the enriched KEGG pathways.

Figure 6

Webserver Statistics (a) Number and type of interactions in the database which were used to construct miRNA-TF-TG co regulatory networks (b) Number of miRNA to disease and miRNA to drug associations.

Figure 7

MyomirDB Statistics (a) Distribution of myomiRs based on level of regulation (Upregulated and Downregulated) in the database. (b) Distribution of myomiRs studied in different source organism. (c) Distribution of myomiRs as per their tissue of expression. (d) Distribution of myomiRs studied as per duration of experiment.

Figure 8

Overview of data collection and annotation in MyomirDB.