epistasis

Deutscher D, Meilijson I, Schuster S & Ruppin E 2008 Can single knockouts accurately single out gene functions? BMC Systems Biol 2:50.

• in non-trivial biological systems single-perturbations will fail to reveal the functional organization of the system, owing to interactions and redundancies
• single-perturbations analysis misses at least 33% of the genes that contribute significantly to the growth potential
• though the essential genes it does find are responsible for most of the growth potential

• when assigning gene contributions for individual metabolic functions, the picture arising from single-perturbations is severely lacking and a multiple-perturbations approach turns out to be essential

• the multiple-perturbations investigation yields a significantly richer and more biologically plausible functional annotation of the genes comprising the metabolic network of the yeast