ISBE – set out for a Systems Biology Infrastructure for Europe

Systems biology requires the availability, co-ordination and simultaneous interaction of a large number of diverse facilities and activities. These cover an entire spectrum, from mathematical modelling, through biological, biomedical and clinical experiments, to dedicated technology development. The systems biology community needs close cooperation with data-generation groups and bioinformaticians to define a strategy for producing life-science data of sufficiently high quality for model generation. For each medical, biological or biotechnological problem addressed, the optimal combination of facilities and activities is likely to be different. The complexity of biological systems, and the diversity and dynamics of their processes, means that a full analysis is far too complex to be handled by a single entity, industry or country – a variety of specialist expertise and facilities are typically necessary to achieve results suitable for modelling. Systems-level approaches for tackling the complexity of life-science data provide a profound conceptual advance compared to reductionist biological research methods of the past. Rather than focusing on individual laboratories, specialising in a limited number of research technologies, the Infrastructure for Systems Biology in Europe (ISBE) will facilitate the synergistic application of a wide range of research techniques and technologies to problems of major medical and biotechnological importance

The need for standardisation in life science research - an approach to excellence and trust

Today, academic researchers benefit from the changes driven by digital technologies and the enormous growth of knowledge and data, on globalisation, enlargement of the scientific community, and the linkage between different scientific communities and the society. To fully benefit from this development, however, information needs to be shared openly and transparently. Digitalisation plays a major role here because it permeates all areas of business, science and society and is one of the key drivers for innovation and international cooperation. To address the resulting opportunities, the EU promotes the development and use of collaborative ways to produce and share knowledge and data as early as possible in the research process, but also to appropriately secure results with the European strategy for Open Science (OS). It is now widely recognised that making research results more accessible to all societal actors contributes to more effective and efficient science; it also serves as a boost for innovation in the public and private sectors. However for research data to be findable, accessible, interoperable and reusable the use of standards is essential. At the metadata level, considerable efforts in standardisation have already been made (e.g. Data Management Plan and FAIR Principle etc.), whereas in context with the raw data these fundamental efforts are still fragmented and in some cases completely missing. The CHARME consortium, funded by the European Cooperation in Science and Technology (COST) Agency, has identified needs and gaps in the field of standardisation in the life sciences and also discussed potential hurdles for implementation of standards in current practice. Here, the authors suggest four measures in response to current challenges to ensure a high quality of life science research data and their re-usability for research and innovation

Large scale automated genome and proteome analysis in plants – GABI-LAPP

Im Rahmen der Technologieplattform GABI-LAPP wird für die pflanzliche Genomforschung Technologie für die Hochdurchsatzanalyse im Proteomics-Bereich entwickelt. Das LAPP-Projekt wird am Ende der Förderperiode eine breite Basis an technologischen Ressourcen für die wissenschaftliche Arbeit an Pflanzen zur Verfügung stellen. Die Methoden werden zunächst an der Modellpflanze Arabidopsis thaliana entwickelt, die Ergebnisse stellen jedoch die Grundlage für angewandte Forschung an Nutzpflanzen, wie z.B. Gerste, dar. Eine zentrale Aufgabe für alle LAPP-Teilprojekte ist die Entwicklung von Hochdurchsatztechnologie für unterschiedliche Arten von Proben und Ansätzen. Diese Entwicklungen sollen die genomweite Analyse von DNA, RNA und Proteinen sowie die Aufklärung von deren Interaktionen ermöglichen. Ausgehend von Arabidopsis werden unterschiedliche Arten von Daten in einer Datenbank erfasst, um durch deren Integration ein großes Potential für angewandte Forschung sowie für Data-Mining zur Verfügung zu stellen. Die LAPP-Teilprojekte sind hauptsächlich am Max-Planck-Institut für molekulare Genetik in Berlin in der Abteilung von Prof. Hans Lehrach angesiedelt

GABI-LAPP - Large-scale Automated Plant Proteomics in GABI

Im Rahmen der Technologieplattform GABI-LAPP wird für die pflanzliche Genomforschung Technologie für die Hochdurchsatzanalyse im Proteomics-Bereich entwickelt. Das LAPP-Projekt wird am Ende der Förderperiode eine breite Basis an technologischen Ressourcen für die wissenschaftliche Arbeit an Pflanzen zur Verfügung stellen. Die Methoden werden zunächst an der Modellpflanze Arabidopsis thaliana entwickelt, die Ergebnisse stellen jedoch die Grundlage für angewandte Forschung an Nutzpflanzen, wie z.B. Gerste, dar. Eine zentrale Aufgabe für alle LAPP-Teilprojekte ist die Entwicklung von Hochdurchsatztechnologie für unterschiedliche Arten von Proben und Ansätzen. Diese Entwicklungen sollen die genomweite Analyse von DNA, RNA und Proteinen sowie die Aufklärung von deren Interaktionen ermöglichen. Ausgehend von Arabidopsis werden unterschiedliche Arten von Daten in einer Datenbank erfasst, um durch deren Integration ein großes Potential für angewandte Forschung sowie für Data-Mining zur Verfügung zu stellen. Die LAPP-Teilprojekte sind hauptsächlich am Max-Planck-Institut für molekulare Genetik in Berlin in der Abteilung von Prof. Hans Lehrach angesiedelt

Ten simple rules on how to write a standard operating procedure

Research publications and data nowadays should be publicly available on the internet and, theoretically, usable for everyone to develop further research, products, or services. The long-term accessibility of research data is, therefore, fundamental in the economy of the research production process. However, the availability of data is not sufficient by itself, but also their quality must be verifiable. Measures to ensure reuse and reproducibility need to include the entire research life cycle, from the experimental design to the generation of data, quality control, statistical analysis, interpretation, and validation of the results. Hence, high-quality records, particularly for providing a string of documents for the verifiable origin of data, are essential elements that can act as a certificate for potential users (customers). These records also improve the traceability and transparency of data and processes, therefore, improving the reliability of results. Standards for data acquisition, analysis, and documentation have been fostered in the last decade driven by grassroot initiatives of researchers and organizations such as the Research Data Alliance (RDA). Nevertheless, what is still largely missing in the life science academic research are agreed procedures for complex routine research workflows. Here, well-crafted documentation like standard operating procedures (SOPs) offer clear direction and instructions specifically designed to avoid deviations as an absolute necessity for reproducibility. Therefore, this paper provides a standardized workflow that explains step by step how to write an SOP to be used as a starting point for appropriate research documentation

Heterologous expression of a ketohexokinase in potato plants leads to inhibited rates of photosynthesis, severe growth retardation and abnormal leaf development

In the present paper we investigated the effect of heterologous expression of a rat liver ketohexokinase in potato (Solanum tuberosum L.) plants with the aim of investigating the role of fructose 1-phosphate in plant metabolism. Plants were generated that contained appreciable activity of ketohexokinase but did not accumulate fructose 1-phosphate. They were, however, characterised by a severe growth retardation and abnormal leaf development. Studies of 14CO2 assimilation and metabolism, and of the levels of photosynthetic pigments, revealed that these lines exhibited restricted photosynthesis. Despite this fact, the levels of starch and soluble sugars remained relatively constant. Analysis of intermediates of starch and sucrose biosynthesis revealed large increases in the triose phosphate and fructose 1,6-bisphosphate pools but relatively unaltered levels of inorganic phosphate and 3-phosphoglycerate, and these lines were also characterised by an accumulation of glyceraldehyde. The transformants neither displayed consistent changes in the activities of Calvin cycle enzymes nor in enzymes of sucrose synthesis but displayed a metabolic profile partially reminiscent of that brought about by end-product limitation, but most likely caused by an inhibition of photosynthesis brought about by the accumulation of glyceraldehyde. Analysis of the metabolite contents in lamina and vein fractions of the leaf, and of the enzymes of carbohydrate oxidation indicate that the phloem-enriched veins of ketohexokinase-expressing leaves tend toward hypoxia and indicate a problem of phloem transport

Inhibition of de Novo Pyrimidine Synthesis in Growing Potato Tubers Leads to a Compensatory Stimulation of the Pyrimidine Salvage Pathway and a Subsequent Increase in Biosynthetic Performance

Pyrimidine nucleotides are of general importance for many aspects of cell function, but their role in the regulation of biosynthetic processes is still unclear. In this study, we investigate the influence of a decreased expression of UMP synthase (UMPS), a key enzyme in the pathway of de novo pyrimidine synthesis, on biosynthetic processes in growing potato (Solanum tuberosum) tubers. Transgenic plants were generated expressing UMPS in the antisense orientation under the control of the tuber-specific patatin promoter. Lines were selected with markedly decreased expression of UMPS in the tubers. Decreased expression of UMPS restricted the use of externally supplied orotate for de novo pyrimidine synthesis in tuber tissue, whereas the uridine-salvaging pathway was stimulated. This shift in the pathways of UMP synthesis was accompanied by increased levels of tuber uridine nucleotides, increased fluxes of [(14)C]sucrose to starch and cell wall synthesis, and increased amounts of starch and cell wall components in the tubers, whereas there were no changes in uridine nucleotide levels in leaves. Decreased expression of UMPS in tubers led to an increase in transcript levels of carbamoylphosphate synthase, uridine kinase, and uracil phosphoribosyltransferase, the latter two encoding enzymes in the pyrimidine salvage pathways. Thus, the results show that antisense inhibition of the de novo pathway of pyrimidine synthesis leads to a compensatory stimulation of the less energy-consuming salvage pathways, probably via increased expression and activity of uridine kinase and uracil phosphoribosyltransferase. This results in increased uridine nucleotide pool levels in tubers and improved biosynthetic performance

The human physiome:How standards, software and innovative service infrastructures are providing the building blocks to make it achievable

Reconstructing and understanding the Human Physiome virtually is a complex mathematical problem, and a highly demanding computational challenge. Mathematical models spanning from the molecular level through to whole populations of individuals must be integrated, then personalized. This requires interoperability with multiple disparate and geographically separated data sources, and myriad computational software tools. Extracting and producing knowledge from such sources, even when the databases and software are readily available, is a challenging task. Despite the difficulties, researchers must frequently perform these tasks so that available knowledge can be continually integrated into the common framework required to realize the Human Physiome. Software and infrastructures that support the communities that generate these, together with their underlying standards to format, describe and interlink the corresponding data and computer models, are pivotal to the Human Physiome being realized. They provide the foundations for integrating, exchanging and re-using data and models efficiently, and correctly, while also supporting the dissemination of growing knowledge in these forms. In this paper, we explore the standards, software tooling, repositories and infrastructures that support this work, and detail what makes them vital to realizing the Human Physiome

The need for standardisation in life science research - an approach to excellence and trust. [version 1; peer review: 3 approved]

Today, academic researchers benefit from the changes driven by digital technologies and the enormous growth of knowledge and data, on globalisation, enlargement of the scientific community, and the linkage between different scientific communities and the society. To fully benefit from this development, however, information needs to be shared openly and transparently. Digitalisation plays a major role here because it permeates all areas of business, science and society and is one of the key drivers for innovation and international cooperation. To address the resulting opportunities, the EU promotes the development and use of collaborative ways to produce and share knowledge and data as early as possible in the research process, but also to appropriately secure results with the European strategy for Open Science (OS). It is now widely recognised that making research results more accessible to all societal actors contributes to more effective and efficient science; it also serves as a boost for innovation in the public and private sectors. However for research data to be findable, accessible, interoperable and reusable the use of standards is essential. At the metadata level, considerable efforts in standardisation have already been made (e.g. Data Management Plan and FAIR Principle etc.), whereas in context with the raw data these fundamental efforts are still fragmented and in some cases completely missing. The CHARME consortium, funded by the European Cooperation in Science and Technology (COST) Agency, has identified needs and gaps in the field of standardisation in the life sciences and also discussed potential hurdles for implementation of standards in current practice. Here, the authors suggest four measures in response to current challenges to ensure a high quality of life science research data and their re-usability for research and innovation