NF-κB- and p50 homodimer DNA-binding sites in genes differentially expressed in the PFC of human alcoholics compared to control subjects [14] were analyzed with the Prometheus system [41]. Transcription Factor (TF) Binding Sites (TFBS) were identified in phylogenetically conserved (human versus rat) regions of the 10 kb-promoter region. The weight matrices for TFBS identification were taken from JASPAR [42]. Prometheus uses the GeneLynx Database [43] and the GeneLynx application programming interface to obtain the genomic coordinates and sequences for human and rat species with an upstream promoter length of 10 kb. LAGAN aligner algorithm was run using a max gap length of 5 bp, a conservation rate of 45 bp, conservation super rate of 65 bp and a score cutoff of 25 bp [44], [45]. The TFBS finding algorithms were run using a window size of 50 bp, a conservation cutoff of 70% and a TF score threshold of 80% for human-rat comparison. The system uses the Grid computing paradigm [46] for the execution of computationally intensive steps involved in the TFBS finding process: genomic sequence alignment and TFBS searching.
