title: Ontology-based literature mining of E. coli vaccine-associated gene interaction networks.
abstract: BACKGROUND
  Pathogenic Escherichia coli infections cause various diseases in humans and many animal species. However, with extensive E. coli vaccine research, we are still unable to fully protect ourselves against E. coli infections. To more rational development of effective and safe E. coli vaccine, it is important to better understand E. coli vaccine-associated gene interaction networks.
  
  
  METHODS
  In this study, we first extended the Vaccine Ontology (VO) to semantically represent various E. coli vaccines and genes used in the vaccine development. We also normalized E. coli gene names compiled from the annotations of various E. coli strains using a pan-genome-based annotation strategy. The Interaction Network Ontology (INO) includes a hierarchy of various interaction-related keywords useful for literature mining. Using VO, INO, and normalized E. coli gene names, we applied an ontology-based SciMiner literature mining strategy to mine all PubMed abstracts and retrieve E. coli vaccine-associated E. coli gene interactions. Four centrality metrics (i.e., degree, eigenvector, closeness, and betweenness) were calculated for identifying highly ranked genes and interaction types.
  
  
  RESULTS
  Using vaccine-related PubMed abstracts, our study identified 11,350 sentences that contain 88 unique INO interactions types and 1,781 unique E. coli genes. Each sentence contained at least one interaction type and two unique E. coli genes. An E. coli gene interaction network of genes and INO interaction types was created. From this big network, a sub-network consisting of 5 E. coli vaccine genes, including carA, carB, fimH, fepA, and vat, and 62 other E. coli genes, and 25 INO interaction types was identified. While many interaction types represent direct interactions between two indicated genes, our study has also shown that many of these retrieved interaction types are indirect in that the two genes participated in the specified interaction process in a required but indirect process. Our centrality analysis of these gene interaction networks identified top ranked E. coli genes and 6 INO interaction types (e.g., regulation and gene expression).
  
  
  CONCLUSIONS
  Vaccine-related E. coli gene-gene interaction network was constructed using ontology-based literature mining strategy, which identified important E. coli vaccine genes and their interactions with other genes through specific interaction types.
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, 58202, USA. junguk.hur@med.und.edu.
authors.forename: Junguk
authors.identifier: http://orcid.org/0000-0002-0736-2149
authors.initials: J
authors.lastname: Hur
authors.affiliation: Department of Computer Engineering, Bogazici University, Istanbul, 34342, Turkey.
authors.forename: Arzucan
authors.initials: A
authors.lastname: Özgür
authors.affiliation: Department of Microbiology and Immunology, Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. yongqunh@med.umich.edu.|Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. yongqunh@med.umich.edu.|Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. yongqunh@med.umich.edu.|Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. yongqunh@med.umich.edu.
authors.forename: Yongqun
authors.initials: Y
authors.lastname: He
mesh_terms: D001428:Bacterial Vaccines / Q000276:immunology*; D064229:Biological Ontologies; D057225:Data Mining / Q000379:methods*; D004926:Escherichia coli / Q000235:genetics* / Q000276:immunology*; D053263:Gene Regulatory Networks; D023281:Genomics
chemical_list: D001428:Bacterial Vaccines