The status of causality in biological databases: data resources and data retrieval possibilities to support logical modeling.

Causal molecular interactions represent key building blocks used in computational modeling, where they facilitate the assembly of regulatory networks. Logical regulatory networks can be used to predict biological and cellular behaviors by system perturbations and in silico simulations. Today, broad sets of causal interactions are available in a variety of biological knowledge resources. However, different visions, based on distinct biological interests, have led to the development of multiple ways to describe and annotate causal molecular interactions. It can therefore be challenging to efficiently explore various resources of causal interaction and maintain an overview of recorded contextual information that ensures valid use of the data. This review lists the different types of public resources with causal interactions, the different views on biological processes that they represent, the various data formats they use for data representation and storage, and the data exchange and conversion procedures that are available to extract and download these interactions. This may further raise awareness among the targeted audience, i.e. logical modelers and other scientists interested in molecular causal interactions, but also database managers and curators, about the abundance and variety of causal molecular interaction data, and the variety of tools and approaches to convert them into one interoperable resource.

SBGN Bricks Ontology as a tool to describe recurring concepts in molecular networks.

A comprehensible representation of a molecular network is key to communicating and understanding scientific results in systems biology. The Systems Biology Graphical Notation (SBGN) has emerged as the main standard to represent such networks graphically. It has been implemented by different software tools, and is now largely used to communicate maps in scientific publications. However, learning the standard, and using it to build large maps, can be tedious. Moreover, SBGN maps are not grounded on a formal semantic layer and therefore do not enable formal analysis. Here, we introduce a new set of patterns representing recurring concepts encountered in molecular networks, called SBGN bricks. The bricks are structured in a new ontology, the Bricks Ontology (BKO), to define clear semantics for each of the biological concepts they represent. We show the usefulness of the bricks and BKO for both the template-based construction and the semantic annotation of molecular networks. The SBGN bricks and BKO can be freely explored and downloaded at sbgnbricks.org.

Setting the basis of best practices and standards for curation and annotation of logical models in biology-highlights of the [BC]2 2019 CoLoMoTo/SysMod Workshop.

The fast accumulation of biological data calls for their integration, analysis and exploitation through more systematic approaches. The generation of novel, relevant hypotheses from this enormous quantity of data remains challenging. Logical models have long been used to answer a variety of questions regarding the dynamical behaviours of regulatory networks. As the number of published logical models increases, there is a pressing need for systematic model annotation, referencing and curation in community-supported and standardised formats. This article summarises the key topics and future directions of a meeting entitled 'Annotation and curation of computational models in biology', organised as part of the 2019 [BC]2 conference. The purpose of the meeting was to develop and drive forward a plan towards the standardised annotation of logical models, review and connect various ongoing projects of experts from different communities involved in the modelling and annotation of molecular biological entities, interactions, pathways and models. This article defines a roadmap towards the annotation and curation of logical models, including milestones for best practices and minimum standard requirements.

UniBioDicts: Unified access to Biological Dictionaries.

SUMMARY: We present a set of software packages that provide uniform access to diverse biological vocabulary resources that are instrumental for current biocuration efforts and tools. The Unified Biological Dictionaries (UniBioDicts or UBDs) provide a single query-interface for accessing the online API services of leading biological data providers. Given a search string, UBDs return a list of matching term, identifier and metadata units from databases (e.g. UniProt), controlled vocabularies (e.g. PSI-MI) and ontologies (e.g. GO, via BioPortal). This functionality can be connected to input fields (user-interface components) that offer autocomplete lookup for these dictionaries. UBDs create a unified gateway for accessing life science concepts, helping curators find annotation terms across resources (based on descriptive metadata and unambiguous identifiers), and helping data users search and retrieve the right query terms. AVAILABILITY AND IMPLEMENTATION: The UBDs are available through npm and the code is available in the GitHub organisation UniBioDicts (https://github.com/UniBioDicts) under the Affero GPL license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Minimum Information about a Molecular Interaction CAusal STatement (MI2CAST).

MOTIVATION: A large variety of molecular interactions occurs between biomolecular components in cells. When a molecular interaction results in a regulatory effect, exerted by one component onto a downstream component, a so-called 'causal interaction' takes place. Causal interactions constitute the building blocks in our understanding of larger regulatory networks in cells. These causal interactions and the biological processes they enable (e.g. gene regulation) need to be described with a careful appreciation of the underlying molecular reactions. A proper description of this information enables archiving, sharing and reuse by humans and for automated computational processing. Various representations of causal relationships between biological components are currently used in a variety of resources. RESULTS: Here, we propose a checklist that accommodates current representations, called the Minimum Information about a Molecular Interaction CAusal STatement (MI2CAST). This checklist defines both the required core information, as well as a comprehensive set of other contextual details valuable to the end user and relevant for reusing and reproducing causal molecular interaction information. The MI2CAST checklist can be used as reporting guidelines when annotating and curating causal statements, while fostering uniformity and interoperability of the data across resources. AVAILABILITY AND IMPLEMENTATION: The checklist together with examples is accessible at https://github.com/MI2CAST/MI2CAST. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Harmonizing semantic annotations for computational models in biology.

Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-readable links to knowledge resource terms, semantic annotations describe the computational or biological meaning of what models and data represent. These annotations help researchers find and repurpose models, accelerate model composition and enable knowledge integration across model repositories and experimental data stores. However, realizing the potential benefits of semantic annotation requires the development of model annotation standards that adhere to a community-based annotation protocol. Without such standards, tool developers must account for a variety of annotation formats and approaches, a situation that can become prohibitively cumbersome and which can defeat the purpose of linking model elements to controlled knowledge resource terms. Currently, no consensus protocol for semantic annotation exists among the larger biological modeling community. Here, we report on the landscape of current annotation practices among the COmputational Modeling in BIology NEtwork community and provide a set of recommendations for building a consensus approach to semantic annotation.

STON: exploring biological pathways using the SBGN standard and graph databases.

BACKGROUND: When modeling in Systems Biology and Systems Medicine, the data is often extensive, complex and heterogeneous. Graphs are a natural way of representing biological networks. Graph databases enable efficient storage and processing of the encoded biological relationships. They furthermore support queries on the structure of biological networks. RESULTS: We present the Java-based framework STON (SBGN TO Neo4j). STON imports and translates metabolic, signalling and gene regulatory pathways represented in the Systems Biology Graphical Notation into a graph-oriented format compatible with the Neo4j graph database. CONCLUSION: STON exploits the power of graph databases to store and query complex biological pathways. This advances the possibility of: i) identifying subnetworks in a given pathway; ii) linking networks across different levels of granularity to address difficulties related to incomplete knowledge representation at single level; and iii) identifying common patterns between pathways in the database.

FAIRification of health-related data using semantic web technologies in the Swiss Personalized Health Network.

The Swiss Personalized Health Network (SPHN) is a government-funded initiative developing federated infrastructures for a responsible and efficient secondary use of health data for research purposes in compliance with the FAIR principles (Findable, Accessible, Interoperable and Reusable). We built a common standard infrastructure with a fit-for-purpose strategy to bring together health-related data and ease the work of both data providers to supply data in a standard manner and researchers by enhancing the quality of the collected data. As a result, the SPHN Resource Description Framework (RDF) schema was implemented together with a data ecosystem that encompasses data integration, validation tools, analysis helpers, training and documentation for representing health metadata and data in a consistent manner and reaching nationwide data interoperability goals. Data providers can now efficiently deliver several types of health data in a standardised and interoperable way while a high degree of flexibility is granted for the various demands of individual research projects. Researchers in Switzerland have access to FAIR health data for further use in RDF triplestores.

Exploring the evolution of biochemical models at the network level.

The evolution of biochemical models is difficult to track. At present, it is not possible to inspect the differences between model versions at the network level. Biochemical models are often constructed in a distributed, non-linear process: collaborators create model versions on different branches from novel information, model extensions, during curation and adaption. To discuss and align the versions, it is helpful to abstract the changes to the network level. The differences between two model versions can be detected by the software tool BiVeS. However, it cannot show the structural changes resulting from the differences. Here, we present a method to visualise the differences between model versions effectively. We developed a JSON schema to communicate the differences at the network level and extended BiVeS accordingly. Additionally, we developed DiVil, a web-based tool to represent the model and the differences as a standardised network using D3. It combines an automatic layout with an interactive user interface to improve the visualisation and to inspect the model. The network can be exported in standardised formats as images or markup language. Our method communicates the structural differences between model versions. It facilitates the discussion of changes and thus supports the collaborative and non-linear nature of model development. Availability and implementation: DiVil prototype: https://divil.bio.informatik.uni-rostock.de, Code on GitHub: https://github.com/Gebbi8/DiVil, licensed under Apache License 2.0. Contact: url="tom.gebhardt@uni-rostock.de.