TY - GEN A1 - Arvidsson, Samuel Janne A1 - Kwasniewski, Miroslaw A1 - Riaño- Pachón, Diego Mauricio A1 - Mueller-Roeber, Bernd T1 - QuantPrime BT - a flexible tool for reliable high-throughput primer design for quantitative PCR T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Background Medium- to large-scale expression profiling using quantitative polymerase chain reaction (qPCR) assays are becoming increasingly important in genomics research. A major bottleneck in experiment preparation is the design of specific primer pairs, where researchers have to make several informed choices, often outside their area of expertise. Using currently available primer design tools, several interactive decisions have to be made, resulting in lengthy design processes with varying qualities of the assays. Results Here we present QuantPrime, an intuitive and user-friendly, fully automated tool for primer pair design in small- to large-scale qPCR analyses. QuantPrime can be used online through the internet http://www.quantprime.de/ or on a local computer after download; it offers design and specificity checking with highly customizable parameters and is ready to use with many publicly available transcriptomes of important higher eukaryotic model organisms and plant crops (currently 295 species in total), while benefiting from exon-intron border and alternative splice variant information in available genome annotations. Experimental results with the model plant Arabidopsis thaliana, the crop Hordeum vulgare and the model green alga Chlamydomonas reinhardtii show success rates of designed primer pairs exceeding 96%. Conclusion QuantPrime constitutes a flexible, fully automated web application for reliable primer design for use in larger qPCR experiments, as proven by experimental data. The flexible framework is also open for simple use in other quantification applications, such as hydrolyzation probe design for qPCR and oligonucleotide probe design for quantitative in situ hybridization. Future suggestions made by users can be easily implemented, thus allowing QuantPrime to be developed into a broad-range platform for the design of RNA expression assays. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 943 KW - prime pair KW - genome annotation KW - specific prime pair KW - primer pair design KW - quantification protocol Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-431531 SN - 1866-8372 IS - 943 ER - TY - GEN A1 - Margaria, Tiziana A1 - Kubczak, Christian A1 - Steffen, Bernhard T1 - Bio-jETI BT - a service integration, design, and provisioning platform for orchestrated bioinformatics processes T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Background: With Bio-jETI, we introduce a service platform for interdisciplinary work on biological application domains and illustrate its use in a concrete application concerning statistical data processing in R and xcms for an LC/MS analysis of FAAH gene knockout. Methods: Bio-jETI uses the jABC environment for service-oriented modeling and design as a graphical process modeling tool and the jETI service integration technology for remote tool execution. Conclusions: As a service definition and provisioning platform, Bio-jETI has the potential to become a core technology in interdisciplinary service orchestration and technology transfer. Domain experts, like biologists not trained in computer science, directly define complex service orchestrations as process models and use efficient and complex bioinformatics tools in a simple and intuitive way. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 822 KW - fatty acid amide hydrolase KW - composite service KW - service orchestration KW - rest service KW - electronic tool integration Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-428868 IS - 822 ER - TY - GEN A1 - Dworschak, Steve A1 - Grell, Susanne A1 - Nikiforova, Victoria J. A1 - Schaub, Torsten H. A1 - Selbig, Joachim T1 - Modeling biological networks by action languages via answer set programming T2 - Postprints der Universität Potsdam : Mathematisch Naturwissenschaftliche Reihe N2 - We describe an approach to modeling biological networks by action languages via answer set programming. To this end, we propose an action language for modeling biological networks, building on previous work by Baral et al. We introduce its syntax and semantics along with a translation into answer set programming, an efficient Boolean Constraint Programming Paradigm. Finally, we describe one of its applications, namely, the sulfur starvation response-pathway of the model plant Arabidopsis thaliana and sketch the functionality of our system and its usage. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 843 KW - biological network model KW - action language KW - answer set programming Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-429846 SN - 1866-8372 IS - 843 ER - TY - GEN A1 - Andorf, Sandra A1 - Gärtner, Tanja A1 - Steinfath, Matthias A1 - Witucka-Wall, Hanna A1 - Altmann, Thomas A1 - Repsilber, Dirk T1 - Towards systems biology of heterosis BT - a hypothesis about molecular network structure applied for the Arabidopsis metabolome T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - We propose a network structure-based model for heterosis, and investigate it relying on metabolite profiles from Arabidopsis. A simple feed-forward two-layer network model (the Steinbuch matrix) is used in our conceptual approach. It allows for directly relating structural network properties with biological function. Interpreting heterosis as increased adaptability, our model predicts that the biological networks involved show increasing connectivity of regulatory interactions. A detailed analysis of metabolite profile data reveals that the increasing-connectivity prediction is true for graphical Gaussian models in our data from early development. This mirrors properties of observed heterotic Arabidopsis phenotypes. Furthermore, the model predicts a limit for increasing hybrid vigor with increasing heterozygosity—a known phenomenon in the literature. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 949 KW - partial correlation KW - biological network KW - metabolite profile KW - molecular network KW - significant edge Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-436274 SN - 1866-8372 IS - 949 ER - TY - GEN A1 - Lamprecht, Anna-Lena A1 - Margaria, Tiziana A1 - Steffen, Bernhard A1 - Sczyrba, Alexander A1 - Hartmeier, Sven A1 - Giegerich, Robert T1 - GeneFisher-P BT - variations of GeneFisher as processes in Bio-jETI T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Background: PCR primer design is an everyday, but not trivial task requiring state-of-the-art software. We describe the popular tool GeneFisher and explain its recent restructuring using workflow techniques. We apply a service-oriented approach to model and implement GeneFisher-P, a process-based version of the GeneFisher web application, as a part of the Bio-jETI platform for service modeling and execution. We show how to introduce a flexible process layer to meet the growing demand for improved user-friendliness and flexibility. Results: Within Bio-jETI, we model the process using the jABC framework, a mature model-driven, service-oriented process definition platform. We encapsulate remote legacy tools and integrate web services using jETI, an extension of the jABC for seamless integration of remote resources as basic services, ready to be used in the process. Some of the basic services used by GeneFisher are in fact already provided as individual web services at BiBiServ and can be directly accessed. Others are legacy programs, and are made available to Bio-jETI via the jETI technology. The full power of service-based process orientation is required when more bioinformatics tools, available as web services or via jETI, lead to easy extensions or variations of the basic process. This concerns for instance variations of data retrieval or alignment tools as provided by the European Bioinformatics Institute (EBI). Conclusions: The resulting service-and process-oriented GeneFisher-P demonstrates how basic services from heterogeneous sources can be easily orchestrated in the Bio-jETI platform and lead to a flexible family of specialized processes tailored to specific tasks. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 868 KW - Basic Service KW - European Bioinformatics Institute KW - Computation Tree Logic KW - Polymerase Chain Reaction Experiment KW - Input Validation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-434241 SN - 1866-8372 IS - 868 ER - TY - GEN A1 - Repsilber, Dirk A1 - Kern, Sabine A1 - Telaar, Anna A1 - Walzl, Gerhard A1 - Black, Gillian F. A1 - Selbig, Joachim A1 - Parida, Shreemanta K. A1 - Kaufmann, Stefan H. E. A1 - Jacobsen, Marc T1 - Biomarker discovery in heterogeneous tissue samples BT - taking the in-silico deconfounding approach T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Background: For heterogeneous tissues, such as blood, measurements of gene expression are confounded by relative proportions of cell types involved. Conclusions have to rely on estimation of gene expression signals for homogeneous cell populations, e.g. by applying micro-dissection, fluorescence activated cell sorting, or in-silico deconfounding. We studied feasibility and validity of a non-negative matrix decomposition algorithm using experimental gene expression data for blood and sorted cells from the same donor samples. Our objective was to optimize the algorithm regarding detection of differentially expressed genes and to enable its use for classification in the difficult scenario of reversely regulated genes. This would be of importance for the identification of candidate biomarkers in heterogeneous tissues. Results: Experimental data and simulation studies involving noise parameters estimated from these data revealed that for valid detection of differential gene expression, quantile normalization and use of non-log data are optimal. We demonstrate the feasibility of predicting proportions of constituting cell types from gene expression data of single samples, as a prerequisite for a deconfounding-based classification approach. Classification cross-validation errors with and without using deconfounding results are reported as well as sample-size dependencies. Implementation of the algorithm, simulation and analysis scripts are available. Conclusions: The deconfounding algorithm without decorrelation using quantile normalization on non-log data is proposed for biomarkers that are difficult to detect, and for cases where confounding by varying proportions of cell types is the suspected reason. In this case, a deconfounding ranking approach can be used as a powerful alternative to, or complement of, other statistical learning approaches to define candidate biomarkers for molecular diagnosis and prediction in biomedicine, in realistically noisy conditions and with moderate sample sizes. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 854 KW - differential gene expression KW - quantile normalization KW - heterogeneous tissue KW - gene expression matrix KW - homogeneous cell population KW - selection KW - microdissection Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-429343 SN - 1866-8372 IS - 854 ER - TY - GEN A1 - Margaria, Tiziana A1 - Steffen, Bernhard A1 - Kubczak, Christian T1 - Evolution support in heterogeneous service-oriented landscapes T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - We present an approach that provides automatic or semi-automatic support for evolution and change management in heterogeneous legacy landscapes where (1) legacy heterogeneous, possibly distributed platforms are integrated in a service oriented fashion, (2) the coordination of functionality is provided at the service level, through orchestration, (3) compliance and correctness are provided through policies and business rules, (4) evolution and correctness-by-design are supported by the eXtreme Model Driven Development paradigm (XMDD) offered by the jABC (Margaria and Steffen in Annu. Rev. Commun. 57, 2004)—the model-driven service oriented development platform we use here for integration, design, evolution, and governance. The artifacts are here semantically enriched, so that automatic synthesis plugins can field the vision of Enterprise Physics: knowledge driven business process development for the end user. We demonstrate this vision along a concrete case study that became over the past three years a benchmark for Semantic Web Service discovery and mediation. We enhance the Mediation Scenario of the Semantic Web Service Challenge along the 2 central evolution paradigms that occur in practice: (a) Platform migration: platform substitution of a legacy system by an ERP system and (b) Backend extension: extension of the legacy Customer Relationship Management (CRM) and Order Management System (OMS) backends via an additional ERP layer. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 918 KW - evolving systems KW - semantic web services KW - service mediation KW - web services KW - SOA Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-432405 SN - 1866-8372 IS - 918 ER - TY - GEN A1 - Gebser, Martin A1 - Kaminski, Roland A1 - Schaub, Torsten H. T1 - Complex optimization in answer set programming T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Preference handling and optimization are indispensable means for addressing nontrivial applications in Answer Set Programming (ASP). However, their implementation becomes difficult whenever they bring about a significant increase in computational complexity. As a consequence, existing ASP systems do not offer complex optimization capacities, supporting, for instance, inclusion-based minimization or Pareto efficiency. Rather, such complex criteria are typically addressed by resorting to dedicated modeling techniques, like saturation. Unlike the ease of common ASP modeling, however, these techniques are rather involved and hardly usable by ASP laymen. We address this problem by developing a general implementation technique by means of meta-prpogramming, thus reusing existing ASP systems to capture various forms of qualitative preferences among answer sets. In this way, complex preferences and optimization capacities become readily available for ASP applications. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 554 KW - answer set programming KW - preference handling KW - complex optimization KW - meta-programming Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-412436 SN - 1866-8372 IS - 554 ER - TY - GEN A1 - Gebser, Martin A1 - Schaub, Torsten H. A1 - Thiele, Sven A1 - Veber, Philippe T1 - Detecting inconsistencies in large biological networks with answer set programming T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - We introduce an approach to detecting inconsistencies in large biological networks by using answer set programming. To this end, we build upon a recently proposed notion of consistency between biochemical/genetic reactions and high-throughput profiles of cell activity. We then present an approach based on answer set programming to check the consistency of large-scale data sets. Moreover, we extend this methodology to provide explanations for inconsistencies by determining minimal representations of conflicts. In practice, this can be used to identify unreliable data or to indicate missing reactions. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 561 KW - answer set programming KW - bioinformatics KW - consistency KW - diagnosis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-412467 SN - 1866-8372 IS - 561 ER - TY - GEN A1 - Durzinsky, Markus A1 - Marwan, Wolfgang A1 - Ostrowski, Max A1 - Schaub, Torsten H. A1 - Wagler, Annegret T1 - Automatic network reconstruction using ASP T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Building biological models by inferring functional dependencies from experimental data is an important issue in Molecular Biology. To relieve the biologist from this traditionally manual process, various approaches have been proposed to increase the degree of automation. However, available approaches often yield a single model only, rely on specific assumptions, and/or use dedicated, heuristic algorithms that are intolerant to changing circumstances or requirements in the view of the rapid progress made in Biotechnology. Our aim is to provide a declarative solution to the problem by appeal to Answer Set Programming (ASP) overcoming these difficulties. We build upon an existing approach to Automatic Network Reconstruction proposed by part of the authors. This approach has firm mathematical foundations and is well suited for ASP due to its combinatorial flavor providing a characterization of all models explaining a set of experiments. The usage of ASP has several benefits over the existing heuristic algorithms. First, it is declarative and thus transparent for biological experts. Second, it is elaboration tolerant and thus allows for an easy exploration and incorporation of biological constraints. Third, it allows for exploring the entire space of possible models. Finally, our approach offers an excellent performance, matching existing, special-purpose systems. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 560 KW - regulatory networks KW - biological networks KW - answer Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-412419 SN - 1866-8372 IS - 560 ER -