The Importance of Modularity in Bioinformatics Tools

In the last decade the amount of Bioinformatics tools has increased enormously. There are tools to store, analyse, visualize, edit or generate biological data and there are still more in development. Still, the demand for increased functionality in a single piece of software must be balanced by the need for modularity to keep the software maintainable. In complex systems, the conflicting demands of features and maintainability are often solved by plug-in systems.

For example Cytoscape, an open source platform for Complex-Network Analysis and Visualization, is using a plug-in system to allow the extension of the application without changing the core. This not only allows the integration of new functionality without a new release but offers the possibility for other developers to contribute plug-ins which are needed in their research.

Most tools have their own, individual plug-in system to meet the needs of the application. These are often very simple and easy to use. However, the increasing complexity of plug-ins demands more functionality of the plug-in system. We want to reuse components in different contexts, we want to have simple plug-in interfaces and we want to allow communication and dependencies between plug-ins. Many tools implemented in Java are facing these problems and there seems to be a common solution: the integration of an established modularity framework, like OSGi. To our knowledge, a number of developers of bioinformatics tools are already implementing, planning or thinking about the integration of OSGi into their applications, e.g. Cytoscape, Protege, PathVisio, ImageJ, Jalview or Chipster. The adoption of modularity frameworks in the development of bioinformatics applications is steadily increasing and should be considered in the design of new software.

By modularity in the traditional computer science sense, we mean the division of a software application into logical parts with separate concerns. To ease the development of software tools the application is separated into smaller logical parts, which are implemented individually. A set of modules can form a larger application but only if a proper glue is used, OSGi is an example of such a glue. OSGi allows to build an infrastructure into an application to add and use different modules. It provides mechanisms to allow the individual modules to rely on and interact with each other, opening the possibility to put together different modules to solve the problem at hand. Later, modules can be removed and new ones can be added to tackle another problem. As Katy Boerner in her article 'Plug-and-Play Macroscopes' writes, we should 'implement software frameworks that empower domain scientists to assemble their own continuously evolving macroscopes, adding and upgrading existing (and removing obsolete) plug-ins to arrive at a set that is truly relevant for their work'.

Some of these modules are going to be specific for one application but a lot of these modules can actually be reused by other tools. We are talking about general features like the import or export of different file formats, a layout algorithm that could be used by several visualization tools or the lookup in an external online database. Why should every tool implement its own parser or algorithm? Modularity can help to share functionality. There is no need to start from scratch and implement everything anew, thus developers can focus on new and important features.

Adding modularity, or better, a modularity framework to an existing software application is not a trivial task. The developers of Cytoscape are currently undertaking this challenge with the coming version 3. We are also working on the integration of OSGi into our pathway visualization tool PathVisio and we now want to share and compare our experiences, so others can benefit from our discoveries. This will not only help them in making a decision if OSGi is a suitable solution for them but also in the integration process itself

SBFC - The Systems Biology Format Converter Framework

The System Biology Format Converter (SBFC) aims is to provide a generic framework that potentially allows any conversion between two formats. Interoperability between formats is a recurring issue in Systems Biology. Although there are various tools available to convert models from one format to another, most of them have been independently developed and cannot easily be combined, specially to provide support for more formats. The framework is written in Java and can be used as a standalone executable. Recently a prototype has been developed with OSGi to achieve a more modular framework structure. This is a collaborative project and we hope that developers will provide support for more formats by creating new modules. SBFC allows anyone to easily add new converters and to integrate existing converters with a minimum of changes. We will also allow to combine several existing converters

Funding application contents with research, technology development and innovation funding agencies in the Czech Republic

Tato bakalářská práce se zabývá náležitostmi návrhu výzkumného projektu u poskytovatelů podpory vývoje a inovací podle zákona č. 130/2002 Sb. Jejím cílem práce je tyto náležitosti popsat, najít jejich společné prvky a rozdíly, a porovnat je s náležitostmi návrhů projektu Horizon Europe, a s náležitostmi grantové žádosti Nadačního fondu Neuron. V teoretické části je popsán proces účelové podpory podle zákona č. 130/2002 Sb. V praktické části jsou popsány a porovnány náležitosti návrhů projektu ve vybraných veřejných soutěžích Technologické agentury České republiky a Grantové agentury České republiky a porovnány s náležitostmi žádostí u Nadačního fondu Neuron a v programu Horizon Europe. Klíčová slova: výzkum, vývoj a inovace, grantová podpora, program, veřejná soutěž ve výzkumu, vývoji a inovacích, návrh projektuThis thesis is focused on requirements on project proposal for a research, development and innovation support providers according act no. 130/2002 Coll. The aim of this thesis is to describe this requirements, find their common elements and differences, and compare them with the requirements of the Horizon Europe project proposals and with the requirements of the grant application of the Neuron Foundation Fund. The theoretical part describes the process of targeted support act no. 130/2002 Coll. In the practical part, the details of project proposals in selected public competitions of the Technology Agency of the Czech Republic and the Czech science foundation are described and compared with the details of applications to the Neuron Foundation and the Horizon Europe program.Ústav informačních studií a knihovnictvíInstitute of Information Studies and LibrarianshipFilozofická fakultaFaculty of Art

WikiPathways: building research communities on biological pathways.

Here, we describe the development of WikiPathways (http://www.wikipathways.org), a public wiki for pathway curation, since it was first published in 2008. New features are discussed, as well as developments in the community of contributors. New features include a zoomable pathway viewer, support for pathway ontology annotations, the ability to mark pathways as private for a limited time and the availability of stable hyperlinks to pathways and the elements therein. WikiPathways content is freely available in a variety of formats such as the BioPAX standard, and the content is increasingly adopted by external databases and tools, including Wikipedia. A recent development is the use of WikiPathways as a staging ground for centrally curated databases such as Reactome. WikiPathways is seeing steady growth in the number of users, page views and edits for each pathway. To assess whether the community curation experiment can be considered successful, here we analyze the relation between use and contribution, which gives results in line with other wiki projects. The novel use of pathway pages as supplementary material to publications, as well as the addition of tailored content for research domains, is expected to stimulate growth further

CyTargetLinker app update: A flexible solution for network extension in Cytoscape

Here, we present an update of the open-source CyTargetLinker app for Cytoscape ( http://apps.cytoscape.org/apps/cytargetlinker) that introduces new automation features. CyTargetLinker provides a simple interface to extend networks with links to relevant data and/or knowledge extracted from so-called linksets. The linksets are provided on the CyTargetLinker website ( https://cytargetlinker.github.io/) or can be custom-made for specific use cases. The new automation feature enables users to programmatically execute the app's functionality in Cytoscape (command line tool) and with external tools (e.g. R, Jupyter, Python, etc). This allows users to share their analysis workflows and therefore increase repeatability and reproducibility. Three use cases demonstrate automated workflows, combinations with other Cytoscape apps and core Cytoscape functionality. We first extend a protein-protein interaction network created with the stringApp, with compound-target interactions and disease-gene annotations. In the second use case, we created a workflow to load differentially expressed genes from an experimental dataset and extend it with gene-pathway associations. Lastly, we chose an example outside the biological domain and used CyTargetLinker to create an author-article-journal network for the five authors of this manuscript using a two-step extension mechanism. With 400 downloads per month in the last year and nearly 20,000 downloads in total, CyTargetLinker shows the adoption and relevance of the app in the field of network biology. In August 2019, the original publication was cited in 83 articles demonstrating the applicability in biomedical research

Beyond Pathway Analysis: Identification of Active Subnetworks in Rett Syndrome

Pathway and network approaches are valuable tools in analysis and interpretation of large complex omics data. Even in the field of rare diseases, like Rett syndrome, omics data are available, and the maximum use of such data requires sophisticated tools for comprehensive analysis and visualization of the results. Pathway analysis with differential gene expression data has proven to be extremely successful in identifying affected processes in disease conditions. In this type of analysis, pathways from different databases like WikiPathways and Reactome are used as separate, independent entities. Here, we show for the first time how these pathway models can be used and integrated into one large network using the WikiPathways RDF containing all human WikiPathways and Reactome pathways, to perform network analysis on transcriptomics data. This network was imported into the network analysis tool Cytoscape to perform active submodule analysis. Using a publicly available Rett syndrome gene expression dataset from frontal and temporal cortex, classical enrichment analysis, including pathway and Gene Ontology analysis, revealed mainly immune response, neuron specific and extracellular matrix processes. Our active module analysis provided a valuable extension of the analysis prominently showing the regulatory mechanism of MECP2, especially on DNA maintenance, cell cycle, transcription, and translation. In conclusion, using pathway models for classical enrichment and more advanced network analysis enables a more comprehensive analysis of gene expression data and provides novel results

Over-expression of the vitamin D receptor (VDR) induces skeletal muscle hypertrophy

ObjectiveThe Vitamin D receptor (VDR) has been positively associated with skeletal muscle mass, function and regeneration. Mechanistic studies have focused upon loss of the receptor, with in vivo whole-body knockout models demonstrating reduced myofiber size and function, and impaired muscle development. To understand the mechanistic role upregulation of the VDR elicits in muscle mass/health, we studied the impact of VDR over-expression (OE) in vivo, before exploring the importance of VDR expression upon muscle hypertrophy in humans.MethodsWistar rats underwent in vivo electrotransfer (IVE) to over-express the VDR in Tibialis anterior (TA) muscle for 10 days, before comprehensive physiological and metabolic profiling to characterise the influence of VDR-OE on muscle protein synthesis (MPS), anabolic signalling and satellite cell activity. Stable isotope tracer (D2O) techniques were used to assess sub-fraction protein synthesis, alongside RNA-Seq analysis. Finally, human participants underwent 20-wks resistance exercise training, with body composition and transcriptomic analysis.ResultsMuscle VDR-OE yielded total protein and RNA accretion, manifesting in increased myofibre area i.e. hypertrophy. The observed increases in MPS were associated with enhanced anabolic signalling reflecting translational efficiency (e.g. mTOR-signalling), with no effects upon protein breakdown markers being observed. Additionally, RNA-Seq illustrated marked extracellular matrix (ECM) remodeling, while satellite cell content, markers of proliferation and associated cell-cycled related gene-sets were up-regulated. Finally, induction of VDR mRNA correlated with muscle hypertrophy in humans following long-term resistance exercise type training.ConclusionVDR-OE stimulates muscle hypertrophy ostensibly via heightened protein synthesis, translational efficiency, ribosomal expansion and up-regulation of ECM remodelling related gene-sets. Furthermore, VDR expression is a robust marker of the hypertrophic response to resistance exercise in humans. The VDR is a viable target of muscle maintenance through testable Vitamin D molecules, as active molecules and analogs