Ola Spjuth

Bioclipse: an open source workbench for chemo- and bioinformatics

BackgroundThere is a need for software applications that provide users with a complete and extensible toolkit for chemo- and bioinformatics accessible from a single workbench. Commercial packages are expensive and closed source, hence they do not allow end users to modify algorithms and add custom functionality. Existing open source projects are more focused on providing a framework for integrating existing, separately installed bioinformatics packages, rather than providing user-friendly interfaces. No open source chemoinformatics workbench has previously been published, and no sucessful attempts have been made to integrate chemo- and bioinformatics into a single framework.ResultsBioclipse is an advanced workbench for resources in chemo- and bioinformatics, such as molecules, proteins, sequences, spectra, and scripts. It provides 2D-editing, 3D-visualization, file format conversion, calculation of chemical properties, and much more; all fully integrated into a user-friendly desktop application. Editing supports standard functions such as cut and paste, drag and drop, and undo/redo. Bioclipse is written in Java and based on the Eclipse Rich Client Platform with a state-of-the-art plugin architecture. This gives Bioclipse an advantage over other systems as it can easily be extended with functionality in any desired direction.ConclusionBioclipse is a powerful workbench for bio- and chemoinformatics as well as an advanced integration platform. The rich functionality, intuitive user interface, and powerful plugin architecture make Bioclipse the most advanced and user-friendly open source workbench for chemo- and bioinformatics. Bioclipse is released under Eclipse Public License (EPL), an open source license which sets no constraints on external plugin licensing; it is totally open for both open source plugins as well as commercial ones. Bioclipse is freely available at http://www.bioclipse.net.

Proteochemometric modeling of HIV protease susceptibility

BackgroundA major obstacle in treatment of HIV is the ability of the virus to mutate rapidly into drug-resistant variants. A method for predicting the susceptibility of mutated HIV strains to antiviral agents would provide substantial clinical benefit as well as facilitate the development of new candidate drugs. Therefore, we used proteochemometrics to model the susceptibility of HIV to protease inhibitors in current use, utilizing descriptions of the physico-chemical properties of mutated HIV proteases and 3D structural property descriptions for the protease inhibitors. The descriptions were correlated to the susceptibility data of 828 unique HIV protease variants for seven protease inhibitors in current use; the data set comprised 4792 protease-inhibitor combinations.ResultsThe model provided excellent predictability (R2 = 0.92, Q2 = 0.87) and identified general and specific features of drug resistance. The models predictive ability was verified by external prediction in which the susceptibilities to each one of the seven inhibitors were omitted from the data set, one inhibitor at a time, and the data for the six remaining compounds were used to create new models. This analysis showed that the over all predictive ability for the omitted inhibitors was Q2inhibitors= 0.72.ConclusionOur results show that a proteochemometric approach can provide generalized susceptibility predictions for new inhibitors. Our proteochemometric model can directly analyze inhibitor-protease interactions and facilitate treatment selection based on viral genotype. The model is available for public use, and is located at HIV Drug Research Centre.

Bioclipse 2: A scriptable integration platform for the life sciences

BackgroundContemporary biological research integrates neighboring scientific domains to answer complex questions in fields such as systems biology and drug discovery. This calls for tools that are intuitive to use, yet flexible to adapt to new tasks.ResultsBioclipse is a free, open source workbench with advanced features for the life sciences. Version 2.0 constitutes a complete rewrite of Bioclipse, and delivers a stable, scalable integration platform for developers and an intuitive workbench for end users. All functionality is available both from the graphical user interface and from a built-in novel domain-specific language, supporting the scientist in interdisciplinary research and reproducible analyses through advanced visualization of the inputs and the results. New components for Bioclipse 2 include a rewritten editor for chemical structures, a table for multiple molecules that supports gigabyte-sized files, as well as a graphical editor for sequences and alignments.ConclusionBioclipse 2 is equipped with advanced tools required to carry out complex analysis in the fields of bio- and cheminformatics. Developed as a Rich Client based on Eclipse, Bioclipse 2 leverages on todays powerful desktop computers for providing a responsive user interface, but also takes full advantage of the Web and networked (Web/Cloud) services for more demanding calculations or retrieval of data. The fact that Bioclipse 2 is based on an advanced and widely used service platform ensures wide extensibility, making it easy to add new algorithms, visualizations, as well as scripting commands. The intuitive tools for end users and the extensible architecture make Bioclipse 2 ideal for interdisciplinary and integrative research.Bioclipse 2 is released under the Eclipse Public License (EPL), a flexible open source license that allows additional plugins to be of any license. Bioclipse 2 is implemented in Java and supported on all major platforms; Source code and binaries are freely available at http://www.bioclipse.net.

The ChEMBL database as linked open data

BackgroundMaking data available as Linked Data using Resource Description Framework (RDF) promotes integration with other web resources. RDF documents can natively link to related data, and others can link back using Uniform Resource Identifiers (URIs). RDF makes the data machine-readable and uses extensible vocabularies for additional information, making it easier to scale up inference and data analysis.ResultsThis paper describes recent developments in an ongoing project converting data from the ChEMBL database into RDF triples. Relative to earlier versions, this updated version of ChEMBL-RDF uses recently introduced ontologies, including CHEMINF and CiTO; exposes more information from the database; and is now available as dereferencable, linked data. To demonstrate these new features, we present novel use cases showing further integration with other web resources, including Bio2RDF, Chem2Bio2RDF, and ChemSpider, and showing the use of standard ontologies for querying.ConclusionsWe have illustrated the advantages of using open standards and ontologies to link the ChEMBL database to other databases. Using those links and the knowledge encoded in standards and ontologies, the ChEMBL-RDF resource creates a foundation for integrated semantic web cheminformatics applications, such as the presented decision support.

Lessons learned from implementing a national infrastructure in Sweden for storage and analysis of next-generation sequencing data

Analyzing and storing data and results from next-generation sequencing (NGS) experiments is a challenging task, hampered by ever-increasing data volumes and frequent updates of analysis methods and tools. Storage and computation have grown beyond the capacity of personal computers and there is a need for suitable e-infrastructures for processing. Here we describe UPPNEX, an implementation of such an infrastructure, tailored to the needs of data storage and analysis of NGS data in Sweden serving various labs and multiple instruments from the major sequencing technology platforms. UPPNEX comprises resources for high-performance computing, large-scale and high-availability storage, an extensive bioinformatics software suite, up-to-date reference genomes and annotations, a support function with system and application experts as well as a web portal and support ticket system. UPPNEX applications are numerous and diverse, and include whole genome-, de novo- and exome sequencing, targeted resequencing, SNP discovery, RNASeq, and methylation analysis. There are over 300 projects that utilize UPPNEX and include large undertakings such as the sequencing of the flycatcher and Norwegian spruce. We describe the strategic decisions made when investing in hardware, setting up maintenance and support, allocating resources, and illustrate major challenges such as managing data growth. We conclude with summarizing our experiences and observations with UPPNEX to date, providing insights into the successful and less successful decisions made.

XMPP for cloud computing in bioinformatics supporting discovery and invocation of asynchronous web services

BackgroundLife sciences make heavily use of the web for both data provision and analysis. However, the increasing amount of available data and the diversity of analysis tools call for machine accessible interfaces in order to be effective. HTTP-based Web service technologies, like the Simple Object Access Protocol (SOAP) and REpresentational State Transfer (REST) services, are today the most common technologies for this in bioinformatics. However, these methods have severe drawbacks, including lack of discoverability, and the inability for services to send status notifications. Several complementary workarounds have been proposed, but the results are ad-hoc solutions of varying quality that can be difficult to use.ResultsWe present a novel approach based on the open standard Extensible Messaging and Presence Protocol (XMPP), consisting of an extension (IO Data) to comprise discovery, asynchronous invocation, and definition of data types in the service. That XMPP cloud services are capable of asynchronous communication implies that clients do not have to poll repetitively for status, but the service sends the results back to the client upon completion. Implementations for Bioclipse and Taverna are presented, as are various XMPP cloud services in bio- and cheminformatics.ConclusionXMPP with its extensions is a powerful protocol for cloud services that demonstrate several advantages over traditional HTTP-based Web services: 1) services are discoverable without the need of an external registry, 2) asynchronous invocation eliminates the need for ad-hoc solutions like polling, and 3) input and output types defined in the service allows for generation of clients on the fly without the need of an external semantics description. The many advantages over existing technologies make XMPP a highly interesting candidate for next generation online services in bioinformatics.

Open Data, Open Source and Open Standards in chemistry: The Blue Obelisk five years on

BackgroundThe Blue Obelisk movement was established in 2005 as a response to the lack of Open Data, Open Standards and Open Source (ODOSOS) in chemistry. It aims to make it easier to carry out chemistry research by promoting interoperability between chemistry software, encouraging cooperation between Open Source developers, and developing community resources and Open Standards.ResultsThis contribution looks back on the work carried out by the Blue Obelisk in the past 5 years and surveys progress and remaining challenges in the areas of Open Data, Open Standards, and Open Source in chemistry.ConclusionsWe show that the Blue Obelisk has been very successful in bringing together researchers and developers with common interests in ODOSOS, leading to development of many useful resources freely available to the chemistry community.

Use of historic metabolic biotransformation data as a means of anticipating metabolic sites using MetaPrint2D and Bioclipse

BackgroundPredicting metabolic sites is important in the drug discovery process to aid in rapid compound optimisation. No interactive tool exists and most of the useful tools are quite expensive.ResultsHere a fast and reliable method to analyse ligands and visualise potential metabolic sites is presented which is based on annotated metabolic data, described by circular fingerprints. The method is available via the graphical workbench Bioclipse, which is equipped with advanced features in cheminformatics.ConclusionsDue to the speed of predictions (less than 50 ms per molecule), scientists can get real time decision support when editing chemical structures. Bioclipse is a rich client, which means that all calculations are performed on the local computer and do not require network connection. Bioclipse and MetaPrint2D are free for all users, released under open source licenses, and available from http://www.bioclipse.net.

The LCB Data Warehouse

UNLABELLED The Linnaeus Centre for Bioinformatics Data Warehouse (LCB-DWH) is a web-based infrastructure for reliable and secure microarray gene expression data management and analysis that provides an online service for the scientific community. The LCB-DWH is an effort towards a complete system for storage (using the BASE system), analysis and publication of microarray data. Important features of the system include: access to established methods within R/Bioconductor for data analysis, built-in connection to the Gene Ontology database and a scripting facility for automatic recording and re-play of all the steps of the analysis. The service is up and running on a high performance server. At present there are more than 150 registered users. AVAILABILITY An open functional version is available at https://dw.lcb.uu.se/index.phtml?i_login=test. User accounts are created upon request. Additional facilities including plug-ins, user documentation and a password protected data storage system are available from http://www.lcb.uu.se/lcbdw.php

Integrated decision support for assessing chemical liabilities.

Chemical liabilities, such as adverse effects and toxicity, have a major impact on todays drug discovery process. In silico prediction of chemical liabilities is an important approach which can reduce costs and animal testing by complementing or replacing in vitro and in vivo liability models. There is a lack of integrated, extensible decision support systems for chemical liability assessment which run quickly and have easily interpretable results. Here we present a method which integrates similarity searches, structural alerts, and QSAR models which all are available from the Bioclipse workbench. Emphasis has been placed on interpretation of results, and substructures which are important for predictions are highlighted in the original chemical structures. This allows for interactively changing chemical structures with instant visual feedback and can be used for hypothesis testing of single chemical structures as well as compound collections. The system has a clear separation between methods and data, and the extensible architecture enables straightforward extension via addition of more plugins (such as new data sets and computational models). We demonstrate our method on three important safety end points: mutagenicity, carcinogenicity, and aryl hydrocarbon receptor (AhR) activation. Bioclipse and the decision support implementation are free, open source, and available from http://www.bioclipse.net/decision-support .