miRMaid: a unified programming interface for microRNA data resources

Abstract

Background: MicroRNAs (miRNAs) are endogenous small RNAs that play a key role in post-transcriptional regulation of gene expression in animals and plants. The number of known miRNAs has increased rapidly over the years. The current release (version 14.0) of miRBase, the central online repository for miRNA annotation, comprises over 10.000 miRNA precursors from 115 different species. Furthermore, a large number of decentralized online resources are now available, each contributing with important miRNA annotation and information.

Results: We have developed a software framework, designated here as miRMaid, with the goal of integrating miRNA data resources in a uniform web service interface that can be accessed and queried by researchers and, most importantly, by computers. miRMaid is built around data from miRBase and is designed to follow the official miRBase data releases. It exposes miRBase data as inter-connected web services. Third-party miRNA data resources can be modularly integrated as miRMaid plugins or they can loosely couple with miRMaid as individual entities in the World Wide Web. miRMaid is available as a public web service but is also easily installed as a local application. The software framework is freely available under the LGPL open source license for academic and commercial use.

Conclusion: miRMaid is an intuitive and modular software platform designed to unify miRBase and independent miRNA data resources. It enables miRNA researchers to computationally address complex questions involving the multitude of miRNA data resources. Furthermore, miRMaid constitutes a basic framework for further programming in which microRNA-interested bioinformaticians can readily develop their own tools and data sources.

Figure 1

Architecture overview. miRMaid uses a Model-View-controller architecture. The model layer provides object oriented encapsulation of data stored in a relational database. The model layer can be efficiently and directly queried using the Ruby programming language. Each model is additionally exposed as a RESTful web resource. The data returned from a resource URL can be returned as HTML (suitable for web browsers), XML (suitable for computer programs) and for some resources also as FASTA sequence format.

Figure 2

Resource map. Each data model (i.e. 'Precursor') in miRMaid has resource URLs for listing all objects (/precursors) or a single object (/precursors/hsa-mir-21). Relationships (denoted by edges in the figure) between models are captured by nested resource URLs (/matures/hsa-miR-21/papers). A solid circle at the end of an edge denotes a 'many' relationship. For example, a species 'has many' precursors (/species/hsa/precursors), while a precursor is related to only 'one' species (/precursors/hsa-mir-21/species).

Figure 3

Plugin integration. A miRMaid plugin is implemented as an isolated MVC slice (an 'Engine' in the Ruby on Rails framework). The plugin defines its own data models and the relationships between these models. The integration (model and resource relationships) between the miRMaid core framework and the plugin is configured inside the plugin. The core framework provides hooks where a plugin can register itself. In the example above, the miR2Disease plugin defines two data models, M2dDisease and M2dDiseaseLink, where only the M2dDiseaseLink integrates directly with the core framework (a 'one-many' relationship with the Mature data model and resource). The effect of this integration is that M2dDiseaseLink objects are connected to Mature objects and that these relationships can be queried directly through the data models or by using RESTful resource URLs.

Figure 4

RESTful clients. RESTful clients can be implemented in most programming languages. Listed above are two examples in the Ruby and Perl programming languages. Both programs perform the same tasks: getting the 'comment' attribute for the cel-let-7 miRNA precursor and getting the mature miRNA sequences (hsa-miR-21 and hsa-miR-21*) for the hsa-mir-21 miRNA precursor. Both programs use standard libraries to issue HTTP GET requests and to parse the resulting XML documents. The final two examples demonstrate how miRMaid's FASTA sequence rendering capability can be used. We use the R statistical framework [21] and the 'curl' command-line program to issue a HTTP request to retrieve all C. elegans mature sequences in FASTA format.

Figure 5

Ruby data models. In a local miRMaid installation, the data models can be queried directly without the overhead of the HTTP protocol and network communication. The figure lists an interactive Ruby IRB session where the data models are queried to analyze the genomic clustering of human mir-17 family members.