Defining genetic interaction

*Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115;
^†Department of Biochemistry, Stanford University, Stanford, CA 94305;
^‡Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294;
^§Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada M5S 3E1; and
^¶Center for Cancer Systems Biology, Dana–Farber Cancer Institute, 44 Binney Street, Boston, MA 02115

Communicated by David Botstein, Princeton University, Princeton, NJ, December 31, 2007 (received for review October 19, 2007)

View larger version:
- In this window
- In a new window
- Download as PowerPoint Slide
Fig. 1.
Different definitions of genetic interaction lead to different distributions of ε (the deviation of the observed double-mutant fitness from expectation). (A) Distributions from all reproducibly measured pairs from Study J that involve genes with singly deleterious mutations show the Min definition to have a negative bias and clear differences from other definitions. (B) The subset of pairs from A involving genes with minor fitness effects shows no significant differences between definitions. (C) The subset of pairs from A involving genes with moderate fitness effects shows Min to have the most severe bias in ε. (D) The subset of pairs from A involving at least one extreme fitness defect exhibits a positive shift in bias in ε for definitions.
View larger version:
- In this window
- In a new window
- Download as PowerPoint Slide
Fig. 2.
Comparison of Study S synthetic interactions with those of Study T and Study P. a–f contain a Venn diagram characterizing agreement between two sets of interactions, with the sum of numbers equaling the number of pairs tested in both compared studies. a–c compare synthetic genetic interactions derived from Study S using the Min definition (Study S_Min) with those of a Study T (12); (b) Study P_severe (17) (Study P considering only the two more severe synthetic interaction levels) and (c) Study P (17) (interactions at all levels of severity). Note that all 14 interactions of Study T and all eight of the Study P_severe interactions were confirmed, confirmation rates of 100% with a 95% C.I. of 76.7–100% and 63.1–100%, respectively. Furthermore, 53 of the 63 Study P_slight interactions were also identified by Study S_Min (confirmation rate 84.2% with a 95% C.I. of 72.7–92.1%). d–f compare synthetic interactions derived from Study S using the Product definition (Study S_Product) with those derived from (d) Study T, (e) Study P_severe, and (f) Study P. In these comparisons, 13 of 14 Study T interactions were confirmed by Study S_Product (confirmation rate 92.9%, with a 95% C.I. of 66.1–99.8%). By contrast, five of eight Study P_severe were confirmed (confirmation rate 62.5%, with a 95% C.I. of 24.5–91.5%), and only 21 of the 63 Study P_slight synthetic interactions were confirmed (confirmation rate 33.3%, with a 95% C.I. of 22–46.3%).