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

Abstract 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.


Introduction
The "COmputational Modeling in BIology NEtwork" (COMBINE) is an initiative to coordinate the development of the various community standards and formats for computational models [1]. By doing so, it is expected that the federated projects will develop a set of interoperable and non-overlapping standards covering all aspects of modeling in biology.  to the COMBINE standards, associated or related standardisation efforts, and tools using these standards.
Some of the topics covered during the meeting included the latest developments in The meeting provided attendees with the opportunity to learn from experts and enthusiasts in systems biology and related fields. The breakout sessions allowed for in-depth discussions of specific topics, while the tutorials provided hands-on training in the use of the COMBINE standards and related tools.
Overall, COMBINE 2022 was a successful event with more than 100 attendees from around the world, bringing together researchers, developers, and users of the COMBINE standards to collaborate and advance the field of systems biology and related areas.
We would like to thank all participants of COMBINE 2022 for making it an engaging and highly productive event.

Current versions of COMBINE standards
As in the previous special issues in the following we will give a brief overview of all COMBINE standards. When using COMBINE standards, please refer to the following (most up-to-date) specifications. New specifications or updates of existing specifications are highlighted with NEW.

BioPAX (Biological PAthway eXchange)
BioPAX is a standard language for integration, exchange and analysis of biological pathway data. It is expressed in OWL. The current specification is:

CellML
The CellML language is an XML markup language to store and exchange computerbased mathematical models. The current specifications are listed in the following table.
NEW CellML 2.0.1 [10] updates CellML 2.0 [11] with an improved identification of rule statements and corrects errata present in the CellML 2.0 specification.

Associated Standards
Associated standards provide an additional layer of semantics to COMBINE representation formats. The current specifications are:

COMBINE
Archive [39] COMBINE Archive 1.0 [40] OMEX Metadata OMEX Metadata Version 1.2 [41] BioModels.net qualifiers [42] - [43] Identifiers.org URIs [44] - [45] Systems Biology Ontology [46] [external] Bioportal [47] Kinetic Simulation Algorithm [external] Bioportal [48] Ontology [46] A COMBINE archive is a single file bundling the various documents and all relevant information necessary for a modelling and simulation project. The archive is encoded using the Open Modeling EXchange format (OMEX). Each element of an SBML file carries an optional attribute sboTerm which value must be a term from SBO. Each symbol of SBGN is associated with an SBO term.
The Kinetic Simulation Algorithm Ontology (KiSAO) describes existing algorithms and their inter-relationships through their characteristics and parameters. KiSAO is used in SED-ML, which allows simulation software to automatically choose the best algorithm available to perform a simulation and unambiguously refer to it.
The OMEX Metadata Specification is a technical implementation of the community consensus across COMBINE standards to harmonise the way we describe computational models and other resources with metadata [49].