title: The Interaction Network Ontology-supported modeling and mining of complex interactions represented with multiple keywords in biomedical literature.
abstract: BACKGROUND
  The Interaction Network Ontology (INO) logically represents biological interactions, pathways, and networks. INO has been demonstrated to be valuable in providing a set of structured ontological terms and associated keywords to support literature mining of gene-gene interactions from biomedical literature. However, previous work using INO focused on single keyword matching, while many interactions are represented with two or more interaction keywords used in combination.
  
  
  METHODS
  This paper reports our extension of INO to include combinatory patterns of two or more literature mining keywords co-existing in one sentence to represent specific INO interaction classes. Such keyword combinations and related INO interaction type information could be automatically obtained via SPARQL queries, formatted in Excel format, and used in an INO-supported SciMiner, an in-house literature mining program. We studied the gene interaction sentences from the commonly used benchmark Learning Logic in Language (LLL) dataset and one internally generated vaccine-related dataset to identify and analyze interaction types containing multiple keywords. Patterns obtained from the dependency parse trees of the sentences were used to identify the interaction keywords that are related to each other and collectively represent an interaction type.
  
  
  RESULTS
  The INO ontology currently has 575 terms including 202 terms under the interaction branch. The relations between the INO interaction types and associated keywords are represented using the INO annotation relations: 'has literature mining keywords' and 'has keyword dependency pattern'. The keyword dependency patterns were generated via running the Stanford Parser to obtain dependency relation types. Out of the 107 interactions in the LLL dataset represented with two-keyword interaction types, 86 were identified by using the direct dependency relations. The LLL dataset contained 34 gene regulation interaction types, each of which associated with multiple keywords. A hierarchical display of these 34 interaction types and their ancestor terms in INO resulted in the identification of specific gene-gene interaction patterns from the LLL dataset. The phenomenon of having multi-keyword interaction types was also frequently observed in the vaccine dataset.
  
  
  CONCLUSIONS
  By modeling and representing multiple textual keywords for interaction types, the extended INO enabled the identification of complex biological gene-gene interactions represented with multiple keywords.
authors.affiliation: Department of Computer Engineering, Bogazici University, 34342 Istanbul, Turkey.
authors.forename: Arzucan
authors.initials: A
authors.lastname: Özgür
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202 USA.
authors.forename: Junguk
authors.initials: J
authors.lastname: Hur
authors.affiliation: Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109 USA.|Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109 USA.|Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109 USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109 USA.
authors.forename: Yongqun
authors.identifier: 0000-0001-9189-9661
authors.initials: Y
authors.lastname: He
keywords: Gene regulation; Gene-gene interaction; INO; Interaction Network Ontology; Interaction keywords; Interaction types; LLL dataset; Literature mining; SciMiner