TCS is one of the well-known signal transduction system and exists among in nearly all prokaryotes, many Archaea, and eukaryotes such as plants, fungi, and yeasts ( 1 ). In general, the TCS consists of two proteins, a sensor kinase for sensing signals and a response regulator that affects the nurmous cellular regulatory circuits. TCSs play a critical role in regulating virulence, antibiotic resistance, and adaptation ( 2 ). However, the signals and cellular response of the TCSs are complicated. To better understand TCSs, we initiated our development of the community-driven Ontology of Two-Component Systems (OTCS) to represent and integrate various relationships among TCSs, signals, TCSs regulon, and regulons’ role.

The OTCS ontology design follows the Open Biomedical Ontologies (OBO) Foundry principle, and aligns with and reuses terms from the OBO ontology such as the Protein Ontology (PR) and the Ontology of Genes and Genomes (OGG). Protégé 4.3 OWL ontology editor (http:// protege.stanford.edu/) was used for ontology establishment. Ontofox (http://ontofox.hegroup.org/) was used to obtain the related term from different ontologies. The OTCS key term ‘two-component regulatory system’ (OTCS_0000001) is defined as a subclass of RO:system, which is a subclass of ‘material entity’ in the Basic Formal Ontology (BFO). The PhoPQ TCS is a common TCS as shown in many bacteria such as E. coli. PhoPQ TCS is essential for mediateing the adaptation to magnesism limiting condition, stress resistance, and virulence ( 3 ). The PhoPQ includes a sensor protein PhoQ and a response regulator PhoP (Fig 1). More information are also added in OTCS. For example, the genes that encoded TCS proteins are also represented in OTCS. OTCS also defines different roles, such as ‘bacterial sensor role’ that inheres in TCS sensor proteins. As a widely used bacterial model, E. coli includes 30 TCSs. These TCSs, the TCS stimuli, and the TCS effector protein are first represented in OTCS. TCSs in other bacteria are also being added to OTCS. We will also evaluate how OTCS can be used to support TCS comparisons and knowledge discovery. The OTCS project website is located at GitHub:https://github.com/biomedontology/otcs.

We have initiated the development of the OTCS to support systematic and logic representation of TCS with the aim to not only integrate the knowledge of TCS but also systematically elucidate the TCSs regulatory network.

This work was supported by grant 108-2917-I-010-001 from Ministry of Science and Technology of Taiwan.