Dear all, I'm new to ChIP-seq and it bothers me to see such discrepancy in what people use as negative control. I will be using endogenously tagged protein and IP with a commercial anti-HA. I see benefits to using input DNA (like for ChIP-chip), IgG or an untagged strain (mostly restricted to yeast). Using a pre-immune IgG seems like a good idea but the very little IP DNA could be highly biased. In my model (the protist Toxoplasma) I would have the luxury to be able to use an untagged strain. My question is: Is there a publication where people have systematically compared the 3 different methods? If not, shouldn't it be done or am I over-worrying here? Thanks!
@ daler: thanks for the detailed answer. I did not know that the algorithm were specifically designed for control to input. Good idea for the IP-IgG. Do you add IgG to the pre-clear step?