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Yim S, Yu H, Jang D, et al. Annotating activation/inhibition relationships to protein-protein interactions using gene ontology relations. BMC Syst Biol. 2018;12:9doi: 10.1186/s12918-018-0535-4.
Yim, S., Yu, H., Jang, D., & Lee, D. (2018). Annotating activation/inhibition relationships to protein-protein interactions using gene ontology relations. BMC systems biology, 129. https://doi.org/10.1186/s12918-018-0535-4
Yim, Soorin, et al. "Annotating activation/inhibition relationships to protein-protein interactions using gene ontology relations." BMC systems biology vol. 12 (2018): 9. doi: https://doi.org/10.1186/s12918-018-0535-4
Yim S, Yu H, Jang D, Lee D. Annotating activation/inhibition relationships to protein-protein interactions using gene ontology relations. BMC Syst Biol. 2018 Apr 11;12:9. doi: 10.1186/s12918-018-0535-4. PMID: 29671402; PMCID: PMC5907154.
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BMC Syst Biol. 2018 Apr 11;12:9. doi: 10.1186/s12918-018-0535-4.

Annotating activation/inhibition relationships to protein-protein interactions using gene ontology relations.

BMC systems biology

Soorin Yim, Hasun Yu, Dongjin Jang, Doheon Lee

Affiliations

  1. Department of Bio and Brain Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
  2. Bio-Synergy Research Center, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
  3. Department of Bio and Brain Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea. [email protected].
  4. Bio-Synergy Research Center, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea. [email protected].

PMID: 29671402 PMCID: PMC5907154 DOI: 10.1186/s12918-018-0535-4

Abstract

BACKGROUND: Signaling pathways can be reconstructed by identifying 'effect types' (i.e. activation/inhibition) of protein-protein interactions (PPIs). Effect types are composed of 'directions' (i.e. upstream/downstream) and 'signs' (i.e. positive/negative), thereby requiring directions as well as signs of PPIs to predict signaling events from PPI networks. Here, we propose a computational method for systemically annotating effect types to PPIs using relations between functional information of proteins.

RESULTS: We used regulates, positively regulates, and negatively regulates relations in Gene Ontology (GO) to predict directions and signs of PPIs. These relations indicate both directions and signs between GO terms so that we can project directions and signs between relevant GO terms to PPIs. Independent test results showed that our method is effective for predicting both directions and signs of PPIs. Moreover, our method outperformed a previous GO-based method that did not consider the relations between GO terms. We annotated effect types to human PPIs and validated several highly confident effect types against literature. The annotated human PPIs are available in Additional file 2 to aid signaling pathway reconstruction and network biology research.

CONCLUSIONS: We annotated effect types to PPIs by using regulates, positively regulates, and negatively regulates relations in GO. We demonstrated that those relations are effective for predicting not only signs, but also directions of PPIs. The usefulness of those relations suggests their potential applications to other types of interactions such as protein-DNA interactions.

Keywords: Activation; Gene ontology; Inhibition; Protein-protein interaction

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