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With the advent of ultra high-throughput sequencing technologies, increasingly researchers are turning to deep sequencing for gene expression studies. Here we present a set of rigorous methods for normalization, quantification of noise, and co-expression analysis of deep sequencing data. Using these methods on 122 cap analysis of gene expression (CAGE) samples of transcription start sites, we construct genome-wide 'promoteromes' in human and mouse consisting of a three-tiered hierarchy of transcription start sites, transcription start clusters, and transcription start regions.