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. 2014 Aug 13;5:37.
doi: 10.1186/2041-1480-5-37. eCollection 2014.

CLO: The Cell Line Ontology

Free PMC article

CLO: The Cell Line Ontology

Sirarat Sarntivijai et al. J Biomed Semantics. .
Free PMC article


Background: Cell lines have been widely used in biomedical research. The community-based Cell Line Ontology (CLO) is a member of the OBO Foundry library that covers the domain of cell lines. Since its publication two years ago, significant updates have been made, including new groups joining the CLO consortium, new cell line cells, upper level alignment with the Cell Ontology (CL) and the Ontology for Biomedical Investigation, and logical extensions.

Construction and content: Collaboration among the CLO, CL, and OBI has established consensus definitions of cell line-specific terms such as 'cell line', 'cell line cell', 'cell line culturing', and 'mortal' vs. 'immortal cell line cell'. A cell line is a genetically stable cultured cell population that contains individual cell line cells. The hierarchical structure of the CLO is built based on the hierarchy of the in vivo cell types defined in CL and tissue types (from which cell line cells are derived) defined in the UBERON cross-species anatomy ontology. The new hierarchical structure makes it easier to browse, query, and perform automated classification. We have recently added classes representing more than 2,000 cell line cells from the RIKEN BRC Cell Bank to CLO. Overall, the CLO now contains ~38,000 classes of specific cell line cells derived from over 200 in vivo cell types from various organisms.

Utility and discussion: The CLO has been applied to different biomedical research studies. Example case studies include annotation and analysis of EBI ArrayExpress data, bioassays, and host-vaccine/pathogen interaction. CLO's utility goes beyond a catalogue of cell line types. The alignment of the CLO with related ontologies combined with the use of ontological reasoners will support sophisticated inferencing to advance translational informatics development.

Keywords: Anatomy; Cell line; Cell line cell; Cell line cell culturing; Immortal cell line cell; Mortal cell line cell.


Figure 1
Figure 1
The top level CLO hierarchical structure and key ontology terms. Terms imported from other ontologies are indicated by the ontology abbreviations inside parentheses. Terms without an identified source are CLO terms. All the arrows indicate the ‘is_a’ relation except the explicitly labelled ‘has grain’ relation.
Figure 2
Figure 2
CLO cell line design pattern and an example. (A) Generic CLO design pattern. Terms imported from external ontologies are displayed in blue boxes, while CLO-specific terms are displayed in yellow boxes. (B) An example of HeLa cell representation by applying CLO design pattern with extended information obtained from the BAO development (shown in dashed orange boxes) with details of culturing method, cell line modification, and STR profiling. Boxes represent instances, some labelled by the class they are an instance of. The relations used to link the boxes are instance-level relations. In several cases the parent class is also noted in the box using an is_a relation.
Figure 3
Figure 3
Demonstration of restructured CLO cell line cell hierarchy and the application of reasoning. (A) asserted HeLa cell hierarchy. Five intermediate terms between ‘immortal cell line cell’ and ‘HeLa cell’ have been generated in CLO. (B) The SubClass axioms of ‘HeLa cell’. (C) Part of an inferred CLO hierarchy. Compared to the asserted hierarchy in Figure 3A, the term ‘immortal human uterine cervix-derived epithelial cell line cell’ has been inferred as a subclass of ‘immortal human epithelial cell line cell’. (D) The equivalent class definition for ‘immortal human epithelial cell line cell’. (E) The equivalent class definition for ‘immortal human uterine cervix-derived epithelial cell line cell’. The OntoFox tool [9] was used to generate a subset of CLO that includes HeLa cell-related terms. The screenshots were generated using the Protégé OWL editor. The ELK version 0.3.2 ontology reasoner was used for reasoning.
Figure 4
Figure 4
CLO application in modelling the cell line cell-vaccine/pathogen interactions. As reported in a reference [16], the live attenuated B. abortus cattle vaccine strain RB51 positively regulated programmed cell death of RAW264.7 cell, a macrophage cell line cell. However, its wild type virulent strain 2308 negatively regulated the programmed cell death. The infected cells underwent different cellular processes after the interaction with the vaccine or pathogen. All the boxes represent instances, labelled by the class they are an instance of.

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