In many areas of data-driven science, large datasets are generated where the individual data objects are images, matrices, or otherwise have a clear structure. However, these objects can be information-sparse, and a challenge is to efficiently find and work with the most interesting data as early as possible in an analysis pipeline. We have recently proposed a new model for big data management where the internal structure and information of the data are associated with each data object (as opposed to simple metadata). There is then an opportunity for comprehensive data management solutions to account for data-specific internal structure as well as access patterns. In this article, we explore this idea together with our recently proposed hierarchical storage management framework that uses reinforcement learning (RL) for autonomous and dynamic data placement in different tiers in a storage hierarchy. Our case-study is based on four scientific datasets: Protein translocation microscopy images, Airfoil angle of attack meshes, 1000 Genomes sequences, and Phenotypic screening images. The presented results highlight that our framework is optimal and can quickly adapt to new data access requirements. It overall reduces the data processing time, and the proposed autonomous data placement is superior compared to any static or semi-static data placement policies.

Fluorescence staining techniques, such as Cell Painting, together with fluorescence microscopy have proven invaluable for visualizing and quantifying the effects that drugs and other perturbations have on cultured cells. However, fluorescence microscopy is expensive, time-consuming, labor-intensive, and the stains applied can be cytotoxic, interfering with the activity under study. The simplest form of microscopy, brightfield microscopy, lacks these downsides, but the images produced have low contrast and the cellular compartments are difficult to discern. Nevertheless, by harnessing deep learning, these brightfield images may still be sufficient for various predictive purposes. In this study, we compared the predictive performance of models trained on fluorescence images to those trained on brightfield images for predicting the mechanism of action (MoA) of different drugs. We also extracted CellProfiler features from the fluorescence images and used them to benchmark the performance. Overall, we found comparable and largely correlated predictive performance for the two imaging modalities. This is promising for future studies of MoAs in time-lapse experiments for which using fluorescence images is problematic. Explorations based on explainable AI techniques also provided valuable insights regarding compounds that were better predicted by one modality over the other.

Federated machine learning promises to overcome the input privacy challenge in machine learning. By iteratively updating a model on private clients and aggregating these local model updates into a global federated model, private data is incorporated in the federated model without needing to share and expose that data. Several open software projects for federated learning have appeared. Most of them focuses on supporting flexible experimentation with different model aggregation schemes and with different privacy-enhancing technologies. However, there is a lack of open frameworks that focuses on critical distributed computing aspects of the problem such as scalability and resilience. It is a big step to take for a data scientist to go from an experimental sandbox to testing their federated schemes at scale in real-world geographically distributed settings. To bridge this gap we have designed and developed a production-grade hierarchical federated learning framework, FEDn. The framework is specifically designed to make it easy to go from local development in pseudo-distributed mode to horizontally scalable distributed deployments. FEDn both aims to be production grade for industrial applications and a flexible research tool to explore real-world performance of novel federated algorithms and the framework has been used in number of industrial and academic R&D projects. In this paper we present the architecture and implementation of FEDn. We demonstrate the framework's scalability and efficiency in evaluations based on two case-studies representative for a cross-silo and a cross-device use-case respectively.

Large and distributed data sets pose many challenges for machine learning, including requirements on computational resources and training time. One approach is to train multiple models in parallel on subsets of data and aggregate the resulting predictions. Large data sets can then be partitioned into smaller chunks, and for distributed data the need for pooling can be avoided. Combining results from conformal predictors using synergy rules has been shown to have advantageous properties for classification problems. In this paper we extend the methodology to regression problems, and we show that it produces valid and efficient predictors compared to inductive conformal predictors and cross-conformal predictors for 10 different data sets from the UCI machine learning repository using three different machine learning methods. The approach offers a straightforward and compelling alternative to pooling data, such as when working in distributed environments.

MOTIVATION: Cell to cell communication is critical for all multicellular organisms, and single-cell sequencing facilitates the construction of full connectivity graphs between cell types in tissues. Such complex data structures demand novel analysis methods and tools for exploratory analysis. RESULTS: We propose a method to predict the putative ligand-receptor interactions between cell types from single-cell RNA-sequencing data. This is achieved by inferring and incorporating interactions in a multi-directional graph, thereby enabling contextual exploratory analysis. We demonstrate that our approach can detect common and specific interactions between cell types in mouse brain and human tumors, and that these interactions fit with expected outcomes. These interactions also include predictions made with molecular ligands integrating information from several types of genes necessary for ligand production and transport. Our implementation is general and can be appended to any transcriptome analysis pipeline to provide unbiased hypothesis generation regarding ligand to receptor interactions between cell populations or for network analysis in silico. AVAILABILITY AND IMPLEMENTATION: scConnect is open source and available as a Python package at https://github.com/JonETJakobsson/scConnect. scConnect is directly compatible with Scanpy scRNA-sequencing pipelines. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

With the increasing amount of image data collected from biomedical experiments there is an urgent need for smarter and more effective analysis methods. Many scientific questions require analysis of image sub-regions related to some specific biology. Finding such regions of interest (ROIs) at low resolution and limiting the data subjected to final quantification at full resolution can reduce computational requirements and save time. In this paper we propose a three-step pipeline: First, bounding boxes for ROIs are located at low resolution. Next, ROIs are subjected to semantic segmentation into sub-regions at mid-resolution. We also estimate the confidence of the segmented sub-regions. Finally, quantitative measurements are extracted at full resolution. We use deep learning for the first two steps in the pipeline and conformal prediction for confidence assessment. We show that limiting final quantitative analysis to sub-regions with full confidence reduces noise and increases separability of observed biological effects.

Data stream processing frameworks provide reliable and efficient mechanisms for executing complex workflows over large datasets. A common challenge for the majority of currently available streaming frameworks is efficient utilization of resources. Most frameworks use static or semi-static settings for resource utilization that work well for established use cases but lead to marginal improvements for unseen scenarios. Another pressing issue is the efficient processing of large individual objects such as images and matrices typical for scientific datasets. HarmonicIO has proven to be a good solution for streams of relatively large individual objects, as demonstrated in a benchmark comparison with the Apache Spark and Kafka streaming frameworks. We here present an extension of the HarmonicIO framework based on the online bin-packing algorithm. The main focus is to compare different strategies adapted in streaming frameworks for efficient resource utilization. Based on a real world use case from large-scale microscopy pipelines, we compare two different strategies of auto-scaling implemented in the HarmonicIO and Spark Streaming frameworks.

MOTIVATION: Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed using the Kubernetes container orchestrator. RESULTS: We developed a Virtual Research Environment (VRE) which facilitates rapid integration of new tools and developing scalable and interoperable workflows for performing metabolomics data analysis. The environment can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry, one nuclear magnetic resonance spectroscopy and one fluxomics study. We showed that the method scales dynamically with increasing availability of computational resources. We demonstrated that the method facilitates interoperability using integration of the major software suites resulting in a turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, statistics and identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science. AVAILABILITY AND IMPLEMENTATION: The PhenoMeNal consortium maintains a web portal (https://portal.phenomenal-h2020.eu) providing a GUI for launching the Virtual Research Environment. The GitHub repository https://github.com/phnmnl/ hosts the source code of all projects. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Computational biologists face many challenges related to data size, and they need to manage complicated analyses often including multiple stages and multiple tools, all of which must be deployed to modern infrastructures. To address these challenges and maintain reproducibility of results, researchers need (i) a reliable way to run processing stages in any computational environment, (ii) a well-defined way to orchestrate those processing stages and (iii) a data management layer that tracks data as it moves through the processing pipeline. RESULTS: Pachyderm is an open-source workflow system and data management framework that fulfils these needs by creating a data pipelining and data versioning layer on top of projects from the container ecosystem, having Kubernetes as the backbone for container orchestration. We adapted Pachyderm and demonstrated its attractive properties in bioinformatics. A Helm Chart was created so that researchers can use Pachyderm in multiple scenarios. The Pachyderm File System was extended to support block storage. A wrapper for initiating Pachyderm on cloud-agnostic virtual infrastructures was created. The benefits of Pachyderm are illustrated via a large metabolomics workflow, demonstrating that Pachyderm enables efficient and sustainable data science workflows while maintaining reproducibility and scalability. AVAILABILITY AND IMPLEMENTATION: Pachyderm is available from https://github.com/pachyderm/pachyderm. The Pachyderm Helm Chart is available from https://github.com/kubernetes/charts/tree/master/stable/pachyderm. Pachyderm is available out-of-the-box from the PhenoMeNal VRE (https://github.com/phnmnl/KubeNow-plugin) and general Kubernetes environments instantiated via KubeNow. The code of the workflow used for the analysis is available on GitHub (https://github.com/pharmbio/LC-MS-Pachyderm). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The cloud computing paradigm have fundamentally changed the way computational resources are being offered. Although the number of large-scale providers in academia is still relatively small, there is a rapidly increasing interest and adoption of cloud Infrastructure-as-a-Service in the scientific community. The added flexibility in how applications can be implemented compared to traditional batch computing systems is one of the key success factors for the paradigm, and scientific cloud computing promises to increase adoption of simulation and data analysis in scientific communities not traditionally users of large scale e-Infrastructure, the so called ”long tail of science”. In 2014, the Swedish National Infrastructure for Computing (SNIC) initiated a project to investigate the cost and constraints of offering cloud infrastructure for Swedish academia. The aim was to build a platform where academics could evaluate cloud computing for their use-cases. SNIC Science Cloud (SSC) has since then evolved into a national-scale cloud infrastructure based on three geographically distributed regions. In this article we present the SSC vision, architectural details and user stories. We summarize the experiences gained from running a nationalscale cloud facility into ”ten simple rules” for starting up a science cloud project based on OpenStack. We also highlight some key areas that require careful attention in order to offer cloud infrastructure for ubiquitous academic needs and in particular scientific workloads.

OBJECTIVE: We provide an e-Science perspective on the workflow from risk factor discovery and classification of disease to evaluation of personalized intervention programs. As case studies, we use personalized prostate and breast cancer screenings. MATERIALS AND METHODS: We describe an e-Science initiative in Sweden, e-Science for Cancer Prevention and Control (eCPC), which supports biomarker discovery and offers decision support for personalized intervention strategies. The generic eCPC contribution is a workflow with 4 nodes applied iteratively, and the concept of e-Science signifies systematic use of tools from the mathematical, statistical, data, and computer sciences. RESULTS: The eCPC workflow is illustrated through 2 case studies. For prostate cancer, an in-house personalized screening tool, the Stockholm-3 model (S3M), is presented as an alternative to prostate-specific antigen testing alone. S3M is evaluated in a trial setting and plans for rollout in the population are discussed. For breast cancer, new biomarkers based on breast density and molecular profiles are developed and the US multicenter Women Informed to Screen Depending on Measures (WISDOM) trial is referred to for evaluation. While current eCPC data management uses a traditional data warehouse model, we discuss eCPC-developed features of a coherent data integration platform. DISCUSSION AND CONCLUSION: E-Science tools are a key part of an evidence-based process for personalized medicine. This paper provides a structured workflow from data and models to evaluation of new personalized intervention strategies. The importance of multidisciplinary collaboration is emphasized. Importantly, the generic concepts of the suggested eCPC workflow are transferrable to other disease domains, although each disease will require tailored solutions.

Hadoop is a convenient framework in e-Science enabling scalable distributed data analysis. In molecular biology, next-generation sequencing produces vast amounts of data and requires flexible frameworks for constructing analysis pipelines. We extend the popular HTSeq package into the Hadoop realm by introducing massively parallel versions of short read quality assessment as well as functionality to count genes mapped by the short reads. We use the Hadoop-streaming library which allows the components to run in both Hadoop and regular Linux systems and evaluate their performance in two different execution environments: A single node on a computational cluster and a Hadoop cluster in a private cloud. We compare the implementations with Apache Pig showing improved runtime performance of our developed methods. We also inject the components in the graphical platform Cloudgene to simplify user interaction.

Virtual Screening is a technique in chemo informatics used for Drug discovery by searching large libraries of molecule structures. Virtual Screening often uses SVM, a supervised machine learning technique used for regression and classification analysis. Virtual screening using SVM not only involves huge datasets, but it is also compute expensive with a complexity that can grow at least up to O(n2). SVM based applications most commonly use MPI, which becomes complex and impractical with large datasets. As an alternative to MPI, MapReduce, and its different implementations, have been successfully used on commodity clusters for analysis of data for problems with very large datasets. Due to the large libraries of molecule structures in virtual screening, it becomes a good candidate for MapReduce. In this paper we present a MapReduce implementation of SVM based virtual screening, using Spark, an iterative MapReduce programming model. We show that our implementation has a good scaling behaviour and opens up the possibility of using huge public cloud infrastructures efficiently for virtual screening.

Abstract Summary: In this work we present WhichCyp, a tool for prediction of which cytochromes P450 isoforms (among 1A2, 2C9, 2C19, 2D6 and 3A4) a given molecule is likely to inhibit. The models are built from experimental high-throughput data using support vector machines and molecular signatures. Availability: The WhichCyp server is freely available for use on the web at http://drug.ku.dk/whichcyp, where the WhichCyp Java program and source code is also available for download. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

SUMMARY: The previously disclosed QuantMap method for grouping chemicals by biological activity used online services for much of the data gathering and some of the numerical analysis. The present work attempts to streamline this process by using local copies of the databases and in-house analysis. Using computational methods similar or identical to those used in the previous work, a qualitatively equivalent result was found in just a few seconds on the same dataset (collection of 18 drugs). We use the user-friendly Galaxy framework to enable users to analyze their own datasets. Hopefully, this will make the QuantMap method more practical and accessible and help achieve its goals to provide substantial assistance to drug repositioning, pharmacology evaluation and toxicology risk assessment. AVAILABILITY: http://galaxy.predpharmtox.org CONTACT: [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: Bioclipse, a graphical workbench for the life sciences, provides functionality for managing and visualizing life science data. We introduce Bioclipse-R, which integrates Bioclipse and the statistical programming language R. The synergy between Bioclipse and R is demonstrated by the construction of a decision support system for anticancer drug screening and mutagenicity prediction, which shows how Bioclipse-R can be used to perform complex tasks from within a single software system. AVAILABILITY AND IMPLEMENTATION: Bioclipse-R is implemented as a set of Java plug-ins for Bioclipse based on the R-package rj. Source code and binary packages are available from https://github.com/bioclipse and http://www.bioclipse.net/bioclipse-r, respectively. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: The HIV Drug Research Centre (HIVDRC) has established Web services for prediction of drug susceptibility for HIV proteases and reverse transcriptases. The services are based on two proteochemometric models which accepts a protease or reverse transcriptase sequence in amino acid form, and outputs the predicted drug susceptibility values. The predictions are based on a comprehensive analysis where all the relevant inhibitors are included, resulting in models with excellent predictive capabilities. AVAILABILITY AND IMPLEMENTATION: The services are implemented as interoperable Web services (REST and XMPP), with supporting web pages to allow for individual analyses. A set of plugins were also developed which make the services available from the Bioclipse workbench for life science. Services are available at http://www.hivdrc.org/services.

BACKGROUND: Compound profiling and drug screening generates large amounts of data and is generally based on microplate assays. Current information systems used for handling this are mainly commercial, closed source, expensive, and heavyweight and there is a need for a flexible lightweight open system for handling plate design, and validation and preparation of data. RESULTS: A Bioclipse plugin consisting of a client part and a relational database was constructed. A multiple-step plate layout point-and-click interface was implemented inside Bioclipse. The system contains a data validation step, where outliers can be removed, and finally a plate report with all relevant calculated data, including dose-response curves. CONCLUSIONS: Brunn is capable of handling the data from microplate assays. It can create dose-response curves and calculate IC50 values. Using a system of this sort facilitates work in the laboratory. Being able to reuse already constructed plates and plate layouts by starting out from an earlier step in the plate layout design process saves time and cuts down on error sources.

BACKGROUND: Predicting 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. RESULTS: Here 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. CONCLUSIONS: Due 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.

BACKGROUND: The omics fields promise to revolutionize our understanding of biology and biomedicine. However, their potential is compromised by the challenge to analyze the huge datasets produced. Analysis of omics data is plagued by the curse of dimensionality, resulting in imprecise estimates of model parameters and performance. Moreover, the integration of omics data with other data sources is difficult to shoehorn into classical statistical models. This has resulted in ad hoc approaches to address specific problems. RESULTS: We present a general approach to omics data analysis that alleviates these problems. By combining eScience and Bayesian methods, we retrieve scientific information and data from multiple sources and coherently incorporate them into large models. These models improve the accuracy of predictions and offer new insights into the underlying mechanisms. This "eScience-Bayes" approach is demonstrated in two proof-of-principle applications, one for breast cancer prognosis prediction from transcriptomic data and one for protein-protein interaction studies based on proteomic data. CONCLUSIONS: Bayesian statistics provide the flexibility to tailor statistical models to the complex data structures in omics biology as well as permitting coherent integration of multiple data sources. However, Bayesian methods are in general computationally demanding and require specification of possibly thousands of prior distributions. eScience can help us overcome these difficulties. The eScience-Bayes thus approach permits us to fully leverage on the advantages of Bayesian methods, resulting in models with improved predictive performance that gives more information about the underlying biological system.

BACKGROUND: Contemporary 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. RESULTS: Bioclipse 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. CONCLUSION: Bioclipse 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 today's 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.

BACKGROUND: Life 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. RESULTS: We 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. CONCLUSION: XMPP 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.

BACKGROUND: There has been recent concern regarding the inability of predictive modeling approaches to generalize to new data. Some of the problems can be attributed to improper methods for model selection and assessment. Here, we have addressed this issue by introducing a novel and general framework, the C1C2, for simultaneous model selection and assessment. The framework relies on a partitioning of the data in order to separate model choice from model assessment in terms of used data. Since the number of conceivable models in general is vast, it was also of interest to investigate the employment of two automatic search methods, a genetic algorithm and a brute-force method, for model choice. As a demonstration, the C1C2 was applied to simulated and real-world datasets. A penalized linear model was assumed to reasonably approximate the true relation between the dependent and independent variables, thus reducing the model choice problem to a matter of variable selection and choice of penalizing parameter. We also studied the impact of assuming prior knowledge about the number of relevant variables on model choice and generalization error estimates. The results obtained with the C1C2 were compared to those obtained by employing repeated K-fold cross-validation for choosing and assessing a model. RESULTS: The C1C2 framework performed well at finding the true model in terms of choosing the correct variable subset and producing reasonable choices for the penalizing parameter, even in situations when the independent variables were highly correlated and when the number of observations was less than the number of variables. The C1C2 framework was also found to give accurate estimates of the generalization error. Prior information about the number of important independent variables improved the variable subset choice but reduced the accuracy of generalization error estimates. Using the genetic algorithm worsened the model choice but not the generalization error estimates, compared to using the brute-force method. The results obtained with repeated K-fold cross-validation were similar to those produced by the C1C2 in terms of model choice, however a lower accuracy of the generalization error estimates was observed. CONCLUSION: The C1C2 framework was demonstrated to work well for finding the true model within a penalized linear model class and accurately assess its generalization error, even for datasets with many highly correlated independent variables, a low observation-to-variable ratio, and model assumption deviations. A complete separation of the model choice and the model assessment in terms of data used for each task improves the estimates of the generalization error.

BACKGROUND: A 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. RESULTS: The model provided excellent predictability (R2 = 0.92, Q2 = 0.87) and identified general and specific features of drug resistance. The model's 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 Q2 inhibitors = 0.72. CONCLUSION: Our 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.

BACKGROUND: There 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 successful attempts have been made to integrate chemo- and bioinformatics into a single framework. RESULTS: Bioclipse 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. CONCLUSION: Bioclipse 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.

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