Context-based resolution of semantic conflicts in biological pathways

Seyeol Yoon, Jinmyung Jung, Hasun Yu, Mijin Kwon, Sungji Choo, Kyunghyun Park, Dongjin Jang, Sangwoo Kim, Doheon Lee

Interactions between biological entities such as genes, proteins and metabolites, so called pathways, are key features to understand molecular mechanisms of life. As pathway information is being accumulated rapidly through various knowledge resources, there are growing interests in maintaining the integrity of the heterogeneous databases. Here, we defined conflict as a status where two contradictory pieces of evidence (i.e. 'A increases B' and 'A decreases B') coexist in a same pathway. This conflict damages unity so that inference of simulation on the integrated pathway network might be unreliable. We defined rule and rule group. A rule consists of interaction of two entities, meta-relation (increase or decrease), and contexts terms about tissue specificity or environmental conditions. The rules, which have the same interaction, are grouped into a rule group. If the rules don't have a unanimous meta-relation, the rule group and the rules are judged as being conflicting. This analysis revealed that almost 20% of known interactions suffer from conflicting information and conflicting information occurred much more frequently in the literature than the public database. By identifying and resolving the conflicts, we expect that pathway databases can be cleaned and used for better secondary analyses such as gene/protein annotation, network dynamics and qualitative/quantitative simulation.