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Ontology-based representation and analysis of host-Brucella interactions.

Lin Y, Xiang Z, He Y - J Biomed Semantics (2015)

Bottom Line: Brucella-associated cell death processes are represented in IDOBRU.SPARQL queries identified many results that are critical to the host-Brucella interactions.The methods and ontology representations used in our study are generic and can be broadened to study the interactions between hosts and other pathogens.

View Article: PubMed Central - PubMed

Affiliation: Unit of Laboratory Animal Medicine, Department of Microbiology and Immunology, Center for Computational Medicine and Bioinformatics, and Comprehensive Cancer Center, University of Michigan Medical School, 1150 W. Medical Center Dr, Ann Arbor, MI 48109 USA.

ABSTRACT

Background: Biomedical ontologies are representations of classes of entities in the biomedical domain and how these classes are related in computer- and human-interpretable formats. Ontologies support data standardization and exchange and provide a basis for computer-assisted automated reasoning. IDOBRU is an ontology in the domain of Brucella and brucellosis. Brucella is a Gram-negative intracellular bacterium that causes brucellosis, the most common zoonotic disease in the world. In this study, IDOBRU is used as a platform to model and analyze how the hosts, especially host macrophages, interact with virulent Brucella strains or live attenuated Brucella vaccine strains. Such a study allows us to better integrate and understand intricate Brucella pathogenesis and host immunity mechanisms.

Results: Different levels of host-Brucella interactions based on different host cell types and Brucella strains were first defined ontologically. Three important processes of virulent Brucella interacting with host macrophages were represented: Brucella entry into macrophage, intracellular trafficking, and intracellular replication. Two Brucella pathogenesis mechanisms were ontologically represented: Brucella Type IV secretion system that supports intracellular trafficking and replication, and Brucella erythritol metabolism that participates in Brucella intracellular survival and pathogenesis. The host cell death pathway is critical to the outcome of host-Brucella interactions. For better survival and replication, virulent Brucella prevents macrophage cell death. However, live attenuated B. abortus vaccine strain RB51 induces caspase-2-mediated proinflammatory cell death. Brucella-associated cell death processes are represented in IDOBRU. The gene and protein information of 432 manually annotated Brucella virulence factors were represented using the Ontology of Genes and Genomes (OGG) and Protein Ontology (PRO), respectively. Seven inference rules were defined to capture the knowledge of host-Brucella interactions and implemented in IDOBRU. Current IDOBRU includes 3611 ontology terms. SPARQL queries identified many results that are critical to the host-Brucella interactions. For example, out of 269 protein virulence factors related to macrophage-Brucella interactions, 81 are critical to Brucella intracellular replication inside macrophages. A SPARQL query also identified 11 biological processes important for Brucella virulence.

Conclusions: To systematically represent and analyze fundamental host-pathogen interaction mechanisms, we provided for the first time comprehensive ontological modeling of host-pathogen interactions using Brucella as the pathogen model. The methods and ontology representations used in our study are generic and can be broadened to study the interactions between hosts and other pathogens.

No MeSH data available.


Related in: MedlinePlus

Ontological representation of the entrance into macrophage to replication by smooth Brucella (a) and rough Brucella (b)
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Fig2: Ontological representation of the entrance into macrophage to replication by smooth Brucella (a) and rough Brucella (b)

Mentions: Smooth and rough Brucella strains utilize different mechanisms of entry into host cells. The Brucella LPS O polysaccharide is a critical molecule for interaction with lipid rafts within the plasma membrane of a host cell. The lipid rafts mediate the internalization of Brucella by phagocytes and nonprofessional phagocytes in a manner that leads to the development of the replicative niche [28]. The ontological representation of Brucella entry into macrophages and other related processes is shown in Fig. 2.Fig. 2


Ontology-based representation and analysis of host-Brucella interactions.

Lin Y, Xiang Z, He Y - J Biomed Semantics (2015)

Ontological representation of the entrance into macrophage to replication by smooth Brucella (a) and rough Brucella (b)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4594885&req=5

Fig2: Ontological representation of the entrance into macrophage to replication by smooth Brucella (a) and rough Brucella (b)
Mentions: Smooth and rough Brucella strains utilize different mechanisms of entry into host cells. The Brucella LPS O polysaccharide is a critical molecule for interaction with lipid rafts within the plasma membrane of a host cell. The lipid rafts mediate the internalization of Brucella by phagocytes and nonprofessional phagocytes in a manner that leads to the development of the replicative niche [28]. The ontological representation of Brucella entry into macrophages and other related processes is shown in Fig. 2.Fig. 2

Bottom Line: Brucella-associated cell death processes are represented in IDOBRU.SPARQL queries identified many results that are critical to the host-Brucella interactions.The methods and ontology representations used in our study are generic and can be broadened to study the interactions between hosts and other pathogens.

View Article: PubMed Central - PubMed

Affiliation: Unit of Laboratory Animal Medicine, Department of Microbiology and Immunology, Center for Computational Medicine and Bioinformatics, and Comprehensive Cancer Center, University of Michigan Medical School, 1150 W. Medical Center Dr, Ann Arbor, MI 48109 USA.

ABSTRACT

Background: Biomedical ontologies are representations of classes of entities in the biomedical domain and how these classes are related in computer- and human-interpretable formats. Ontologies support data standardization and exchange and provide a basis for computer-assisted automated reasoning. IDOBRU is an ontology in the domain of Brucella and brucellosis. Brucella is a Gram-negative intracellular bacterium that causes brucellosis, the most common zoonotic disease in the world. In this study, IDOBRU is used as a platform to model and analyze how the hosts, especially host macrophages, interact with virulent Brucella strains or live attenuated Brucella vaccine strains. Such a study allows us to better integrate and understand intricate Brucella pathogenesis and host immunity mechanisms.

Results: Different levels of host-Brucella interactions based on different host cell types and Brucella strains were first defined ontologically. Three important processes of virulent Brucella interacting with host macrophages were represented: Brucella entry into macrophage, intracellular trafficking, and intracellular replication. Two Brucella pathogenesis mechanisms were ontologically represented: Brucella Type IV secretion system that supports intracellular trafficking and replication, and Brucella erythritol metabolism that participates in Brucella intracellular survival and pathogenesis. The host cell death pathway is critical to the outcome of host-Brucella interactions. For better survival and replication, virulent Brucella prevents macrophage cell death. However, live attenuated B. abortus vaccine strain RB51 induces caspase-2-mediated proinflammatory cell death. Brucella-associated cell death processes are represented in IDOBRU. The gene and protein information of 432 manually annotated Brucella virulence factors were represented using the Ontology of Genes and Genomes (OGG) and Protein Ontology (PRO), respectively. Seven inference rules were defined to capture the knowledge of host-Brucella interactions and implemented in IDOBRU. Current IDOBRU includes 3611 ontology terms. SPARQL queries identified many results that are critical to the host-Brucella interactions. For example, out of 269 protein virulence factors related to macrophage-Brucella interactions, 81 are critical to Brucella intracellular replication inside macrophages. A SPARQL query also identified 11 biological processes important for Brucella virulence.

Conclusions: To systematically represent and analyze fundamental host-pathogen interaction mechanisms, we provided for the first time comprehensive ontological modeling of host-pathogen interactions using Brucella as the pathogen model. The methods and ontology representations used in our study are generic and can be broadened to study the interactions between hosts and other pathogens.

No MeSH data available.


Related in: MedlinePlus