[BioC] ChIP-Seq Normalization of mutant vs. WT libraries

Minerva Trejo minerva.trejo at slu.se
Mon Jun 2 15:58:42 CEST 2014

Hello everyone,

I work with a ChIP-seq experiment profiling a histone modification in wild type and a mutant. In the mutant we expect a general reduction of the modification. It is possible that in some regions the reduction is more pronounced than in others. We want to test 2 hypotheses: (i) modification levels are lower in the mutant than in the WT. (ii) Reductions in modification levels differ between genomic contexts.
My questions is how to best normalize such data between samples. I am afraid scaling (e.g. based on library size) or quantile normalisation will greatly reduce or even mask the differences between WT and mutant (imagine all peaks are reduced by a factor of 2). Is there a robust method for such cases? Maybe based on a statistical modelling of unspecific background vs. specific signals, where only the latter should be affected in the mutant?
Thank you in advance.

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