Software that goes with the flow in systems biology

A recent article in BMC Bioinformatics describes new advances in workflow systems for computational modeling in systems biology. Such systems can accelerate, and improve the consistency of, modeling through automation not only at the simulation and results-production stages, but also at the model-generation stage. Their work is a harbinger of the next generation of more powerful software for systems biologists

OREMP: Ontology Reasoning Engine for Molecular Pathways

The information about molecular processes is shared continuously in the form of runnable pathway collections, and biomedical ontologies provide a semantic context to the majority of those pathways. Recent advances in both fields pave the way for a scalable information integration based on aggregate knowledge repositories, but the lack of overall standard formats impedes this progress. Here we propose a strategy that integrates these resources by means of extended ontologies built on top of a common meta-format. Information sharing, integration and discovery are the primary features provided by the system; additionally, two current field applications of the system are reported

Management and provision of computational models

Quantitative models of biological systems provide an understanding of chemical and biological phenomena based on their underlying mechanisms. Moreover, they can be used for example, to predict the behaviour of a system under given conditions or direct future experiments. This has made quantitative models the perfect tools to answer a variety of questions in the biological sciences and has lead to a steady growth of the number of published models.

To maximise the benefits of this growing body of models, the field needs centralised model repositories that will encourage, facilitate and promote model dissemination and reuse. BioModels Database(http://www.ebi.ac.uk/biomodels/) has been developed to exactly fulfil those needs. In order to ensure the correctness of the models distributed, their structure and behaviour are thoroughly checked. To ease their understanding, the model elements are annotated with terms from controlled vocabularies as well as linked to relevant data resources. Finally, to allow their reuse, the models are provided encoded in community supported and standardised formats.

However, the modelling field is constantly evolving and data providers, like BioModels Database, are faced with new challenges. For example, models are getting more and more complex (with for instance the availability of whole organism metabolic network reconstructions) and this has a direct impact on the performance of hosting infrastructures and annotation procedures. Also, models are now being developed collaboratively: this requires new methodologies and systems, akin to the ones used in software development (with for example versioned repositories of models). Moreover, very different kinds of models are being developed by diverse communities, but ultimately their data management needs are very similar.

This talk will introduce the needs which lead to the development of BioModels Database, present the resource and its current infrastructure and finally discuss the challenges that we are facing today and the plans to overcome them

OREMPdb: a semantic dictionary of computational pathway models

<p>Abstract</p> <p>Background</p> <p>The information coming from biomedical ontologies and computational pathway models is expanding continuously: research communities keep this process up and their advances are generally shared by means of dedicated resources published on the web. In fact, such models are shared to provide the characterization of molecular processes, while biomedical ontologies detail a semantic context to the majority of those pathways. Recent advances in both fields pave the way for a scalable information integration based on aggregate knowledge repositories, but the lack of overall standard formats impedes this progress. Indeed, having different objectives and different abstraction levels, most of these resources "speak" different languages. Semantic web technologies are here explored as a means to address some of these problems.</p> <p>Methods</p> <p>Employing an extensible collection of interpreters, we developed OREMP (Ontology Reasoning Engine for Molecular Pathways), a system that abstracts the information from different resources and combines them together into a coherent ontology. Continuing this effort we present OREMPdb; once different pathways are fed into OREMP, species are linked to the external ontologies referred and to reactions in which they participate. Exploiting these links, the system builds species-sets, which encapsulate species that operate together. Composing all of the reactions together, the system computes all of the reaction paths from-and-to all of the species-sets.</p> <p>Results</p> <p>OREMP has been applied to the curated branch of BioModels (2011/04/15 release) which overall contains 326 models, 9244 reactions, and 5636 species. OREMPdb is the semantic dictionary created as a result, which is made of 7360 species-sets. For each one of these sets, OREMPdb links the original pathway and the link to the original paper where this information first appeared. </p

Controlled vocabularies and semantics in systems biology

The use of computational modeling to describe and analyze biological systems is at the heart of systems biology. Model structures, simulation descriptions and numerical results can be encoded in structured formats, but there is an increasing need to provide an additional semantic layer. Semantic information adds meaning to components of structured descriptions to help identify and interpret them unambiguously. Ontologies are one of the tools frequently used for this purpose. We describe here three ontologies created specifically to address the needs of the systems biology community. The Systems Biology Ontology (SBO) provides semantic information about the model components. The Kinetic Simulation Algorithm Ontology (KiSAO) supplies information about existing algorithms available for the simulation of systems biology models, their characterization and interrelationships. The Terminology for the Description of Dynamics (TEDDY) categorizes dynamical features of the simulation results and general systems behavior. The provision of semantic information extends a model's longevity and facilitates its reuse. It provides useful insight into the biology of modeled processes, and may be used to make informed decisions on subsequent simulation experiments

MEMOSys: Bioinformatics platform for genome-scale metabolic models

<p>Abstract</p> <p>Background</p> <p>Recent advances in genomic sequencing have enabled the use of genome sequencing in standard biological and biotechnological research projects. The challenge is how to integrate the large amount of data in order to gain novel biological insights. One way to leverage sequence data is to use genome-scale metabolic models. We have therefore designed and implemented a bioinformatics platform which supports the development of such metabolic models.</p> <p>Results</p> <p>MEMOSys (MEtabolic MOdel research and development System) is a versatile platform for the management, storage, and development of genome-scale metabolic models. It supports the development of new models by providing a built-in version control system which offers access to the complete developmental history. Moreover, the integrated web board, the authorization system, and the definition of user roles allow collaborations across departments and institutions. Research on existing models is facilitated by a search system, references to external databases, and a feature-rich comparison mechanism. MEMOSys provides customizable data exchange mechanisms using the SBML format to enable analysis in external tools. The web application is based on the Java EE framework and offers an intuitive user interface. It currently contains six annotated microbial metabolic models.</p> <p>Conclusions</p> <p>We have developed a web-based system designed to provide researchers a novel application facilitating the management and development of metabolic models. The system is freely available at <url>http://www.icbi.at/MEMOSys</url>.</p

BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models

Background: Quantitative models of biochemical and cellular systems are used to answer a variety of questions in the biological sciences. The number of published quantitative models is growing steadily thanks to increasing interest in the use of models as well as the development of improved software systems and the availability of better, cheaper computer hardware. To maximise the benefits of this growing body of models, the field needs centralised model repositories that will encourage, facilitate and promote model dissemination and reuse. Ideally, the models stored in these repositories should be extensively tested and encoded in community-supported and standardised formats. In addition, the models and their components should be cross-referenced with other resources in order to allow their unambiguous identification. Description: BioModels Database http://www.ebi.ac.uk/biomodels/ is aimed at addressing exactly these needs. It is a freely-accessible online resource for storing, viewing, retrieving, and analysing published, peer-reviewed quantitative models of biochemical and cellular systems. The structure and behaviour of each simulation model distributed by BioModels Database are thoroughly checked; in addition, model elements are annotated with terms from controlled vocabularies as well as linked to relevant data resources. Models can be examined online or downloaded in various formats. Reaction network diagrams generated from the models are also available in several formats. BioModels Database also provides features such as online simulation and the extraction of components from large scale models into smaller submodels. Finally, the system provides a range of web services that external software systems can use to access up-to-date data from the database. Conclusions: BioModels Database has become a recognised reference resource for systems biology. It is being used by the community in a variety of ways; for example, it is used to benchmark different simulation systems, and to study the clustering of models based upon their annotations. Model deposition to the database today is advised by several publishers of scientific journals. The models in BioModels Database are freely distributed and reusable; the underlying software infrastructure is also available from SourceForge https://sourceforge.net/projects/biomodels/ under the GNU General Public License

Propagating semantic information in biochemical network models

<p>Abstract</p> <p>Background</p> <p>To enable automatic searches, alignments, and model combination, the elements of systems biology models need to be compared and matched across models. Elements can be identified by machine-readable biological annotations, but assigning such annotations and matching non-annotated elements is tedious work and calls for automation.</p> <p>Results</p> <p>A new method called "semantic propagation" allows the comparison of model elements based not only on their own annotations, but also on annotations of surrounding elements in the network. One may either propagate feature vectors, describing the annotations of individual elements, or quantitative similarities between elements from different models. Based on semantic propagation, we align partially annotated models and find annotations for non-annotated model elements.</p> <p>Conclusions</p> <p>Semantic propagation and model alignment are included in the open-source library semanticSBML, available on sourceforge. Online services for model alignment and for annotation prediction can be used at <url>http://www.semanticsbml.org</url>.</p

Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans

Peer reviewedPublisher PD

Challenges in horizontal model integration

BACKGROUND: Systems Biology has motivated dynamic models of important intracellular processes at the pathway level, for example, in signal transduction and cell cycle control. To answer important biomedical questions, however, one has to go beyond the study of isolated pathways towards the joint study of interacting signaling pathways or the joint study of signal transduction and cell cycle control. Thereby the reuse of established models is preferable, as it will generally reduce the modeling effort and increase the acceptance of the combined model in the field. RESULTS: Obtaining a combined model can be challenging, especially if the submodels are large and/or come from different working groups (as is generally the case, when models stored in established repositories are used). To support this task, we describe a semi-automatic workflow based on established software tools. In particular, two frequent challenges are described: identification of the overlap and subsequent (re)parameterization of the integrated model. CONCLUSIONS: The reparameterization step is crucial, if the goal is to obtain a model that can reproduce the data explained by the individual models. For demonstration purposes we apply our workflow to integrate two signaling pathways (EGF and NGF) from the BioModels Database. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-016-0266-3) contains supplementary material, which is available to authorized users