Much of what we know about gene interactions in development has been learned using nematodes, yeast, flies, and bacteria. This is due, in part, to the relative ease of genetic manipulation of these well-characterized genomes. However, of great interest are gene interactions involving complex diseases in humans. Wang and White [(2011). Nature Methods 8(4):341–346] describe work using RNAi to examine the interactive proteome in mammalian cells. They mention that knockdown inefficiencies and off-target effects of introduced RNAi species are areas that need particular improvement if the methodology is to be fruitful.

Comment on how 'knockdown inefficiencies' and 'off-target effects' would influence the interpretation of results.