Matthias Klapperstück

VANTED v2: a framework for systems biology applications

BackgroundExperimental datasets are becoming larger and increasingly complex, spanning different data domains, thereby expanding the requirements for respective tool support for their analysis. Networks provide a basis for the integration, analysis and visualization of multi-omics experimental datasets.ResultsHere we present Vanted (version 2), a framework for systems biology applications, which comprises a comprehensive set of seven main tasks. These range from network reconstruction, data visualization, integration of various data types, network simulation to data exploration combined with a manifold support of systems biology standards for visualization and data exchange. The offered set of functionalities is instantiated by combining several tasks in order to enable users to view and explore a comprehensive dataset from different perspectives. We describe the system as well as an exemplary workflow.ConclusionsVanted is a stand-alone framework which supports scientists during the data analysis and interpretation phase. It is available as a Java open source tool from http://www.vanted.org

MetaCrop 2.0: managing and exploring information about crop plant metabolism

MetaCrop is a manually curated repository of high-quality data about plant metabolism, providing different levels of detail from overview maps of primary metabolism to kinetic data of enzymes. It contains information about seven major crop plants with high agronomical importance and two model plants. MetaCrop is intended to support research aimed at the improvement of crops for both nutrition and industrial use. It can be accessed via web, web services and an add-on to the Vanted software. Here, we present several novel developments of the MetaCrop system and the extended database content. MetaCrop is now available in version 2.0 at http://metacrop.ipk-gatersleben.de.

Quantitative Multilevel Analysis of Central Metabolism in Developing Oilseeds of Oilseed Rape during in Vitro Culture

Analysis of carbon partitioning in oilseeds underscores a tradeoff between lipid and starch during seed storage synthesis that is not reflected in the proteome. Seeds provide the basis for many food, feed, and fuel products. Continued increases in seed yield, composition, and quality require an improved understanding of how the developing seed converts carbon and nitrogen supplies into storage. Current knowledge of this process is often based on the premise that transcriptional regulation directly translates via enzyme concentration into flux. In an attempt to highlight metabolic control, we explore genotypic differences in carbon partitioning for in vitro cultured developing embryos of oilseed rape (Brassica napus). We determined biomass composition as well as 79 net fluxes, the levels of 77 metabolites, and 26 enzyme activities with specific focus on central metabolism in nine selected germplasm accessions. Overall, we observed a tradeoff between the biomass component fractions of lipid and starch. With increasing lipid content over the spectrum of genotypes, plastidic fatty acid synthesis and glycolytic flux increased concomitantly, while glycolytic intermediates decreased. The lipid/starch tradeoff was not reflected at the proteome level, pointing to the significance of (posttranslational) metabolic control. Enzyme activity/flux and metabolite/flux correlations suggest that plastidic pyruvate kinase exerts flux control and that the lipid/starch tradeoff is most likely mediated by allosteric feedback regulation of phosphofructokinase and ADP-glucose pyrophosphorylase. Quantitative data were also used to calculate in vivo mass action ratios, reaction equilibria, and metabolite turnover times. Compounds like cyclic 3′,5′-AMP and sucrose-6-phosphate were identified to potentially be involved in so far unknown mechanisms of metabolic control. This study provides a rich source of quantitative data for those studying central metabolism.

Transcript abundance on its own cannot be used to infer fluxes in central metabolism

An attempt has been made to define the extent to which metabolic flux in central plant metabolism is reflected by changes in the transcriptome and metabolome, based on an analysis of in vitro cultured immature embryos of two oilseed rape (Brassica napus) accessions which contrast for seed lipid accumulation. Metabolic flux analysis (MFA) was used to constrain a flux balance metabolic model which included 671 biochemical and transport reactions within the central metabolism. This highly confident flux information was eventually used for comparative analysis of flux vs. transcript (metabolite). Metabolite profiling succeeded in identifying 79 intermediates within the central metabolism, some of which differed quantitatively between the two accessions and displayed a significant shift corresponding to flux. An RNA-Seq based transcriptome analysis revealed a large number of genes which were differentially transcribed in the two accessions, including some enzymes/proteins active in major metabolic pathways. With a few exceptions, differential activity in the major pathways (glycolysis, TCA cycle, amino acid, and fatty acid synthesis) was not reflected in contrasting abundances of the relevant transcripts. The conclusion was that transcript abundance on its own cannot be used to infer metabolic activity/fluxes in central plant metabolism. This limitation needs to be borne in mind in evaluating transcriptome data and designing metabolic engineering experiments.

The LAILAPS search engine: relevance ranking in life science databases.

Search engines and retrieval systems are popular tools at a life science desktop. The manual inspection of hundreds of database entries, that reflect a life science concept or fact, is a time intensive daily work. Hereby, not the number of query results matters, but the relevance does. In this paper, we present the LAILAPS search engine for life science databases. The concept is to combine a novel feature model for relevance ranking, a machine learning approach to model user relevance profiles, ranking improvement by user feedback tracking and an intuitive and slim web user interface, that estimates relevance rank by tracking user interactions. Queries are formulated as simple keyword lists and will be expanded by synonyms. Supporting a flexible text index and a simple data import format, LAILAPS can easily be used both as search engine for comprehensive integrated life science databases and for small in-house project databases. With a set of features, extracted from each database hit in combination with user relevance preferences, a neural network predicts user specific relevance scores. Using expert knowledge as training data for a predefined neural network or using users own relevance training sets, a reliable relevance ranking of database hits has been implemented. In this paper, we present the LAILAPS system, the concepts, benchmarks and use cases. LAILAPS is public available for SWISSPROT data at http://lailaps.ipk-gatersleben.de.

LAILAPS: the plant science search engine.

With the number of sequenced plant genomes growing, the number of predicted genes and functional annotations is also increasing. The association between genes and phenotypic traits is currently of great interest. Unfortunately, the information available today is widely scattered over a number of different databases. Information retrieval (IR) has become an all-encompassing bioinformatics methodology for extracting knowledge from complex, heterogeneous and distributed databases, and therefore can be a useful tool for obtaining a comprehensive view of plant genomics, from genes to traits. Here we describe LAILAPS (http://lailaps.ipk-gatersleben.de), an IR system designed to link plant genomic data in the context of phenotypic attributes for a detailed forward genetic research. LAILAPS comprises around 65 million indexed documents, encompassing >13 major life science databases with around 80 million links to plant genomic resources. The LAILAPS search engine allows fuzzy querying for candidate genes linked to specific traits over a loosely integrated system of indexed and interlinked genome databases. Query assistance and an evidence-based annotation system enable time-efficient and comprehensive information retrieval. An artificial neural network incorporating user feedback and behavior tracking allows relevance sorting of results. We fully describe LAILAPS’s functionality and capabilities by comparing this system’s performance with other widely used systems and by reporting both a validation in maize and a knowledge discovery use-case focusing on candidate genes in barley.

Metabolomics, Standards, and Metabolic Modeling for Synthetic Biology in Plants

Life on earth depends on dynamic chemical transformations that enable cellular functions, including electron transfer reactions, as well as synthesis and degradation of biomolecules. Biochemical reactions are coordinated in metabolic pathways that interact in a complex way to allow adequate regulation. Biotechnology, food, biofuel, agricultural, and pharmaceutical industries are highly interested in metabolic engineering as an enabling technology of synthetic biology to exploit cells for the controlled production of metabolites of interest. These approaches have only recently been extended to plants due to their greater metabolic complexity (such as primary and secondary metabolism) and highly compartmentalized cellular structures and functions (including plant-specific organelles) compared with bacteria and other microorganisms. Technological advances in analytical instrumentation in combination with advances in data analysis and modeling have opened up new approaches to engineer plant metabolic pathways and allow the impact of modifications to be predicted more accurately. In this article, we review challenges in the integration and analysis of large-scale metabolic data, present an overview of current bioinformatics methods for the modeling and visualization of metabolic networks, and discuss approaches for interfacing bioinformatics approaches with metabolic models of cellular processes and flux distributions in order to predict phenotypes derived from specific genetic modifications or subjected to different environmental conditions.

ContextuWall: Peer Collaboration Using (Large) Displays

The emerging field of Immersive Analytics investigates how novel display and interaction technologies can enable people to visualise and analyse data and complex information. In this paper, we present ContextuWall, a system for interactive local and remote collaboration using touch and mobile devices as well as displays of various sizes. The system enables groups of users located on different sites to share content to a jointly used virtual desktop which is accessible over a secured network. This virtual desktop can be shown on different large displays simultaneously, taking advantage of their high resolution. To enable users to intuitively share, arrange as well as annotate image content, a purpose-built client software has been built and can easily be adapted with plug-ins for existing data analytics software. We show exemplary use cases and describe the system architecture and its implementation.

Stereoscopic Space Map – Semi-immersive Configuration of 3D-stereoscopic Tours in Multi-display Environments

Although large-scale stereoscopic 3D environments like CAVEs are a favorable location for group presentations, the perspective projection and stereoscopic optimization usually follows a navigator-centric approach. Therefore, these presentations are usually accompanied by strong side-effects, such as motion sickness which is often caused by a disturbed stereoscopic vision. The reason is that the stereoscopic visualization is usually optimized for the only head-tracked person in the CAVE – the navigator – ignoring the needs of the real target group – the audience. To overcome this misconception, this work proposes an alternative to the head tracking-based stereoscopic effect optimization. By using an interactive virtual overview map in 3D, the pre-tour and on-tour configuration of the stereoscopic effect is provided, partly utilizing our previously published interactive projection plane approach. This Stereoscopic Space Map is visualized by the zSpace 200®, whereas the virtual world is shown on a panoramic 330° CAVE2TM. A pilot expert study with eight participants was conducted using pre-configured tours through 3D models. The comparison of the manual and automatic stereoscopic adjustment showed that the proposed approach is an appropriate alternative to the nowadays commonly used head tracking-based stereoscopic adjustment.

A case study for efficient management of high throughput primary lab data

BackgroundIn modern life science research it is very important to have an efficient management of high throughput primary lab data. To realise such an efficient management, four main aspects have to be handled: (I) long term storage, (II) security, (III) upload and (IV) retrieval.FindingsIn this paper we define central requirements for a primary lab data management and discuss aspects of best practices to realise these requirements. As a proof of concept, we introduce a pipeline that has been implemented in order to manage primary lab data at the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK). It comprises: (I) a data storage implementation including a Hierarchical Storage Management system, a relational Oracle Database Management System and a BFiler package to store primary lab data and their meta information, (II) the Virtual Private Database (VPD) implementation for the realisation of data security and the LIMS Light application to (III) upload and (IV) retrieve stored primary lab data.ConclusionsWith the LIMS Light system we have developed a primary data management system which provides an efficient storage system with a Hierarchical Storage Management System and an Oracle relational database. With our VPD Access Control Method we can guarantee the security of the stored primary data. Furthermore the system provides high performance upload and download and efficient retrieval of data.