A digenic genetic interaction (GI) is observed when mutations in two genes within the same organism yield a phenotype that is different from the expected, given each mutations individual effects. While multiplicative scoring is widely applied to define GIs, revealing underlying gene functions, it remains unclear if it is the most suitable choice for scoring GIs in Escherichia coli. Here, we assess many different definitions, including the multiplicative model, for mapping functional links between genes and pathways in E. coli.