GIO Structure (partial) The genetic interaction ontology (GIO) incorporating the genetic interactions structured terminology (GIST) Genetic Interaction: Phenotype Modification vs. Unexpected Whereas many published definitions of “genetic interaction” assert that there must be a deviation from an expected double perturbation phenotype1-4, many examples of genetic interactions in the literature and in biological databases5-7 include phenotype modifications like suppression or enhancement that are not necessarily reported with an expected double perturbation trait value, precluding an analysis of expectation or deviation from it. For this reason, this genetic interaction ontology has two terms for genetic interaction distinguished by their meanings as either “sensu phenotype modification” or “sensu unexpected”. Both types of interactions provide meaningful insights into the biology of the genes in question, yet they have distinct sets of conclusions that can be drawn from them. This will be important for future curation and interpretation of genetic interactions catalogued by genetic interaction databases. References 1. Eddy SR. Genetics. Total information awareness for worm genetics. Science. 2006 Mar 10;311(5766):1381-2. PubMed PMID: 16527956. 2. Mani R, St Onge RP, Hartman JL 4th, Giaever G, Roth FP. Defining genetic interaction. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3461-6. doi: 10.1073/pnas.0712255105. Epub 2008 Feb 27. PubMed PMID: 18305163; PubMed Central PMCID: PMC2265146. 3. Dixon SJ, Costanzo M, Baryshnikova A, Andrews B, Boone C. Systematic mapping of genetic interaction networks. Annu Rev Genet. 2009;43:601-25. doi: 10.1146/annurev.genet.39.073003.114751. Review. PubMed PMID: 19712041. 4. Baryshnikova A, Costanzo M, Myers CL, Andrews B, Boone C. Genetic interaction networks: toward an understanding of heritability. Annu Rev Genomics Hum Genet. 2013;14:111-33. doi: 10.1146/annurev-genom-082509-141730. Epub 2013 Jun 26. Review. PubMed PMID: 23808365. 5. Harris TW, Arnaboldi V, Cain S, Chan J, Chen WJ, Cho J, Davis P, Gao S, Grove CA, Kishore R, Lee RYN, Muller HM, Nakamura C, Nuin P, Paulini M, Raciti D, Rodgers FH, Russell M, Schindelman G, Auken KV, Wang Q, Williams G, Wright AJ, Yook K, Howe KL, Schedl T, Stein L, Sternberg PW. WormBase: a modern Model Organism Information Resource. Nucleic Acids Res. 2020 Jan 8;48(D1):D762-D767. doi: 10.1093/nar/gkz920. PubMed PMID: 31642470. 6. Oughtred R, Stark C, Breitkreutz BJ, Rust J, Boucher L, Chang C, Kolas N, O'Donnell L, Leung G, McAdam R, Zhang F, Dolma S, Willems A, Coulombe-Huntington J, Chatr-Aryamontri A, Dolinski K, Tyers M. The BioGRID interaction database: 2019 update. Nucleic Acids Res. 2019 Jan 8;47(D1):D529-D541. doi: 10.1093/nar/gky1079. PubMed PMID: 30476227; PubMed Central PMCID: PMC6324058. 7. Thurmond J, Goodman JL, Strelets VB, Attrill H, Gramates LS, Marygold SJ, Matthews BB, Millburn G, Antonazzo G, Trovisco V, Kaufman TC, Calvi BR; FlyBase Consortium . FlyBase 2.0: the next generation. Nucleic Acids Res. 2019 Jan 8;47(D1):D759-D765. doi: 10.1093/nar/gky1003. PubMed PMID: 30364959; PubMed Central PMCID: PMC6323960. 8. Grove CA, Oughtred RW, Lee R, Dolinski K, Tyers M, Sternberg P, Baryshnikova A. Genetic Interactions Structured Terminology (GIST): A new standard for describing and annotating cross-species genetic interactions data. Biocuration 2017, Stanford University, Stanford CA. 9. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000 May;25(1):25-9. PubMed PMID: 10802651; PubMed Central PMCID: PMC3037419. 10. The Gene Ontology Consortium. The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res. 2019 Jan 8;47(D1):D330-D338. doi: 10.1093/nar/gky1055. PubMed