A formal perturbation equation describing the genotypephenotype relationship was proposed ( 48 ) to compute the fitness effect , or Evolutionary Action ( EA ) , of mutations . This equation is a product between the size of a mutation and the functional sensitivity at the position being mutated . EA quantified the likely functional impact of individual mutations on par or better than other methods in blind and objective assessments ( 49 ) , and also helped in the interpretation of exome data ( 50 ) , ignoring any interaction effects . Newer methods have begun to integrate EA over entire populations of mutations in cohorts of patients ( 51 - 54 ) , Cohort Integral ( CI ) ( 55 ) . These attempts sum the separate effects of individual mutational steps to identify genes for specific traits or diseases . None , however , capture interaction epistasis effects , which we now try to do with application to the low mutational frequency of cancer driver genes .