[BioC] Single nucleotide based RNAseq normalization with edgeR?

[Jens Georg]

Dear edgeR users and developers,

we used Solexa sequencing in order to detect RNase E processing sites. 
Therefor we splitted a RNA sample and treated one half with RNase E 
prior to cDNA synthesis and sequencing. The libraries differ in size 
(1.918.953 and 1.208.586 reads respectively) which clearly necessitates 
a normalization step. Furthermore we expect site specific differences 
rather than differences in the accumulation of the full length RNAs.

So I want to ask, if it is appropiate to do a single nucleotide based 
normalization with edgeR and do you think a reliable basic normalization 
is possible without replicates?

Thank you for your comments.

Best regards

Jens