Could the strategy help researchers to get more information from their screens by identifying synergistic effects between genes?
This is a potential problem and an advantage. The potential problem in the approach is that RNAi against 2 or more genes using the multiplex could change the phenotypic effects so that they differ from those you would see if you were targeting the genes individually. This may mean that the effects of some gene targets may be masked in the context of a multiplex leading to a false negative result. Alternatively it also has the potential that you could see proteins that act synergistically. It’s a double-edged sword. In our work, we clearly saw some of those synergistic effects and I think if you were very specifically looking for that, it could be quite informative. How did you avoid unwanted off-target effects, which could cause false positive results, in your screens? False positives arising from off-target effects will occur regardless of whether you are using a multiplex or an array format. The only way a multiplex would give a higher rate of false positives is where the sum effects
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