Towards an Interoperability Landscape for a National Research Data Infrastructure for Personal Health Data.

The German initiative "National Research Data Infrastructure for Personal Health Data" (NFDI4Health) focuses on research data management in health research. It aims to foster and develop harmonized informatics standards for public health, epidemiological studies, and clinical trials, facilitating access to relevant data and metadata standards. This publication lists syntactic and semantic data standards of potential use for NFDI4Health and beyond, based on interdisciplinary meetings and workshops, mappings of study questionnaires and the NFDI4Health metadata schema, and literature search. Included are 7 syntactic, 32 semantic and 9 combined syntactic and semantic standards. In addition, 101 ISO Standards from ISO/TC 215 Health Informatics and ISO/TC 276 Biotechnology could be identified as being potentially relevant. The work emphasizes the utilization of standards for epidemiological and health research data ensuring interoperability as well as the compatibility to NFDI4Health, its use cases, and to (inter-)national efforts within these sectors. The goal is to foster collaborative and inter-sectoral work in health research and initiate a debate around the potential of using common standards.

Toward a common standard for data and specimen provenance in life sciences.

Open and practical exchange, dissemination, and reuse of specimens and data have become a fundamental requirement for life sciences research. The quality of the data obtained and thus the findings and knowledge derived is thus significantly influenced by the quality of the samples, the experimental methods, and the data analysis. Therefore, a comprehensive and precise documentation of the pre-analytical conditions, the analytical procedures, and the data processing are essential to be able to assess the validity of the research results. With the increasing importance of the exchange, reuse, and sharing of data and samples, procedures are required that enable cross-organizational documentation, traceability, and non-repudiation. At present, this information on the provenance of samples and data is mostly either sparse, incomplete, or incoherent. Since there is no uniform framework, this information is usually only provided within the organization and not interoperably. At the same time, the collection and sharing of biological and environmental specimens increasingly require definition and documentation of benefit sharing and compliance to regulatory requirements rather than consideration of pure scientific needs. In this publication, we present an ongoing standardization effort to provide trustworthy machine-actionable documentation of the data lineage and specimens. We would like to invite experts from the biotechnology and biomedical fields to further contribute to the standard.

Bringing Communities Together: Mapping the Investigation-Study-Assay-Model (ISA) to Fast Healthcare Interoperability Resources (FHIR).

Adhering to FAIR principles (findability, accessibility, interoperability, reusability) ensures sustainability and reliable exchange of data and metadata. Research communities need common infrastructures and information models to collect, store, manage and work with data and metadata. The German initiative NFDI4Health created a metadata schema and an infrastructure integrating existing platforms based on different information models and standards. To ensure system compatibility and enhance data integration possibilities, we mapped the Investigation-Study-Assay (ISA) model to Fast Healthcare Interoperability Resources (FHIR). We present the mapping in FHIR logical models, a resulting FHIR resources' network and challenges that we encountered. Challenges mainly related to ISA's genericness, and to different structures and datatypes used in ISA and FHIR. Mapping ISA to FHIR is feasible but requires further analyses of example data and adaptations to better specify target FHIR elements, and enable possible automatized conversions from ISA to FHIR.

Specifications of standards in systems and synthetic biology: status and developments in 2022 and the COMBINE meeting 2022.

This special issue of the Journal of Integrative Bioinformatics contains updated specifications of COMBINE standards in systems and synthetic biology. The 2022 special issue presents three updates to the standards: CellML 2.0.1, SBML Level 3 Package: Spatial Processes, Version 1, Release 1, and Synthetic Biology Open Language (SBOL) Version 3.1.0. This document can also be used to identify the latest specifications for all COMBINE standards. In addition, this editorial provides a brief overview of the COMBINE 2022 meeting in Berlin.

Computational Models for Clinical Applications in Personalized Medicine-Guidelines and Recommendations for Data Integration and Model Validation.

The future development of personalized medicine depends on a vast exchange of data from different sources, as well as harmonized integrative analysis of large-scale clinical health and sample data. Computational-modelling approaches play a key role in the analysis of the underlying molecular processes and pathways that characterize human biology, but they also lead to a more profound understanding of the mechanisms and factors that drive diseases; hence, they allow personalized treatment strategies that are guided by central clinical questions. However, despite the growing popularity of computational-modelling approaches in different stakeholder communities, there are still many hurdles to overcome for their clinical routine implementation in the future. Especially the integration of heterogeneous data from multiple sources and types are challenging tasks that require clear guidelines that also have to comply with high ethical and legal standards. Here, we discuss the most relevant computational models for personalized medicine in detail that can be considered as best-practice guidelines for application in clinical care. We define specific challenges and provide applicable guidelines and recommendations for study design, data acquisition, and operation as well as for model validation and clinical translation and other research areas.

Systems Biology in ELIXIR: modelling in the spotlight.

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR's future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.

Improving the FAIRness of Health Studies in Germany: The German Central Health Study Hub COVID-19.

The German Central Health Study Hub COVID-19 is an online service that offers bundled access to COVID-19 related studies conducted in Germany. It combines metadata and other information of epidemiologic, public health and clinical studies into a single data repository for FAIR data access. In addition to study characteristics the system also allows easy access to study documents, as well as instruments for data collection. Study metadata and survey instruments are decomposed into individual data items and semantically enriched to ease the findability. Data from existing clinical trial registries (DRKS, clinicaltrails.gov and WHO ICTRP) are merged with epidemiological and public health studies manually collected and entered. More than 850 studies are listed as of September 2021.

Specifications of standards in systems and synthetic biology: status and developments in 2021.

This special issue of the Journal of Integrative Bioinformatics contains updated specifications of COMBINE standards in systems and synthetic biology. The 2021 special issue presents four updates of standards: Synthetic Biology Open Language Visual Version 2.3, Synthetic Biology Open Language Visual Version 3.0, Simulation Experiment Description Markup Language Level 1 Version 4, and OMEX Metadata specification Version 1.2. This document can also be consulted to identify the latest specifications of all COMBINE standards.

[Making COVID-19 research data more accessible-building a nationwide information infrastructure]. / COVID-19-Forschungsdaten leichter zugänglich machen ­ Aufbau einer bundesweiten Informationsinfrastruktur.

Public health research and epidemiological and clinical studies are necessary to understand the COVID-19 pandemic and to take appropriate action. Therefore, since early 2020, numerous research projects have also been initiated in Germany. However, due to the large amount of information, it is currently difficult to get an overview of the diverse research activities and their results. Based on the "Federated research data infrastructure for personal health data" (NFDI4Health) initiative, the "COVID-19 task force" is able to create easier access to SARS-CoV-2- and COVID-19-related clinical, epidemiological, and public health research data. Therefore, the so-called FAIR data principles (findable, accessible, interoperable, reusable) are taken into account and should allow an expedited communication of results. The most essential work of the task force includes the generation of a study portal with metadata, selected instruments, other study documents, and study results as well as a search engine for preprint publications. Additional contents include a concept for the linkage between research and routine data, a service for an enhanced practice of image data, and the application of a standardized analysis routine for harmonized quality assessment. This infrastructure, currently being established, will facilitate the findability and handling of German COVID-19 research. The developments initiated in the context of the NFDI4Health COVID-19 task force are reusable for further research topics, as the challenges addressed are generic for the findability of and the handling with research data.

Facilitating Study and Item Level Browsing for Clinical and Epidemiological COVID-19 Studies.

COVID-19 poses a major challenge to individuals and societies around the world. Yet, it is difficult to obtain a good overview of studies across different medical fields of research such as clinical trials, epidemiology, and public health. Here, we describe a consensus metadata model to facilitate structured searches of COVID-19 studies and resources along with its implementation in three linked complementary web-based platforms. A relational database serves as central study metadata hub that secures compatibilities with common trials registries (e.g. ICTRP and standards like HL7 FHIR, CDISC ODM, and DataCite). The Central Search Hub was developed as a single-page application, the other two components with additional frontends are based on the SEEK platform and MICA, respectively. These platforms have different features concerning cohort browsing, item browsing, and access to documents and other study resources to meet divergent user needs. By this we want to promote transparent and harmonized COVID-19 research.

Towards standardization guidelines for in silico approaches in personalized medicine.

Despite the ever-progressing technological advances in producing data in health and clinical research, the generation of new knowledge for medical benefits through advanced analytics still lags behind its full potential. Reasons for this obstacle are the inherent heterogeneity of data sources and the lack of broadly accepted standards. Further hurdles are associated with legal and ethical issues surrounding the use of personal/patient data across disciplines and borders. Consequently, there is a need for broadly applicable standards compliant with legal and ethical regulations that allow interpretation of heterogeneous health data through in silico methodologies to advance personalized medicine. To tackle these standardization challenges, the Horizon2020 Coordinating and Support Action EU-STANDS4PM initiated an EU-wide mapping process to evaluate strategies for data integration and data-driven in silico modelling approaches to develop standards, recommendations and guidelines for personalized medicine. A first step towards this goal is a broad stakeholder consultation process initiated by an EU-STANDS4PM workshop at the annual COMBINE meeting (COMBINE 2019 workshop report in same issue). This forum analysed the status quo of data and model standards and reflected on possibilities as well as challenges for cross-domain data integration to facilitate in silico modelling approaches for personalized medicine.

The first 10 years of the international coordination network for standards in systems and synthetic biology (COMBINE).

This paper presents a report on outcomes of the 10th Computational Modeling in Biology Network (COMBINE) meeting that was held in Heidelberg, Germany, in July of 2019. The annual event brings together researchers, biocurators and software engineers to present recent results and discuss future work in the area of standards for systems and synthetic biology. The COMBINE initiative coordinates the development of various community standards and formats for computational models in the life sciences. Over the past 10 years, COMBINE has brought together standard communities that have further developed and harmonized their standards for better interoperability of models and data. COMBINE 2019 was co-located with a stakeholder workshop of the European EU-STANDS4PM initiative that aims at harmonized data and model standardization for in silico models in the field of personalized medicine, as well as with the FAIRDOM PALs meeting to discuss findable, accessible, interoperable and reusable (FAIR) data sharing. This report briefly describes the work discussed in invited and contributed talks as well as during breakout sessions. It also highlights recent advancements in data, model, and annotation standardization efforts. Finally, this report concludes with some challenges and opportunities that this community will face during the next 10 years.

Specifications of standards in systems and synthetic biology: status and developments in 2020.

This special issue of the Journal of Integrative Bioinformatics presents papers related to the 10th COMBINE meeting together with the annual update of COMBINE standards in systems and synthetic biology.

Data Management in Computational Systems Biology: Exploring Standards, Tools, Databases, and Packaging Best Practices.

Computational systems biology involves integrating heterogeneous datasets in order to generate models. These models can assist with understanding and prediction of biological phenomena. Generating datasets and integrating them into models involves a wide range of scientific expertise. As a result these datasets are often collected by one set of researchers, and exchanged with others researchers for constructing the models. For this process to run smoothly the data and models must be FAIR-findable, accessible, interoperable, and reusable. In order for data and models to be FAIR they must be structured in consistent and predictable ways, and described sufficiently for other researchers to understand them. Furthermore, these data and models must be shared with other researchers, with appropriately controlled sharing permissions, before and after publication. In this chapter we explore the different data and model standards that assist with structuring, describing, and sharing. We also highlight the popular standards and sharing databases within computational systems biology.

Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2019.

This special issue of the Journal of Integrative Bioinformatics presents an overview of COMBINE standards and their latest specifications. The standards cover representation formats for computational modeling in synthetic and systems biology and include BioPAX, CellML, NeuroML, SBML, SBGN, SBOL and SED-ML. The articles in this issue contain updated specifications of SBGN Process Description Level 1 Version 2, SBML Level 3 Core Version 2 Release 2, SBOL Version 2.3.0, and SBOL Visual Version 2.1.

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.

Correction to: Meeting report from the fourth meeting of the Computational Modeling in Biology Network (COMBINE).

[This corrects the article DOI: 10.4056/sigs.5279417.].

Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2017.

Standards are essential to the advancement of Systems and Synthetic Biology. COMBINE provides a formal body and a centralised platform to help develop and disseminate relevant standards and related resources. The regular special issue of the Journal of Integrative Bioinformatics aims to support the exchange, distribution and archiving of these standards by providing unified, easily citable access. This paper provides an overview of existing COMBINE standards and presents developments of the last year.