Szymon M. Kielbasa (firstname.lastname@example.org)
Nils Blüthgen (email@example.com)
Christine Sers (firstname.lastname@example.org)
Reinhold Schäfer (email@example.com)
Hanspeter Herzel (firstname.lastname@example.org)
Institute for Theoretical Biology,
Humboldt University, Berlin, Germany
Institute of Pathology, Charité, Humboldt University, Berlin, Germany
We present a computational pipeline to predict cis-regulatory elements
composing results based on different algorithms: Clover, Cluster-Buster, an own
implementation of human/rat/mouse sequence identity and our ITB algorithm. The
procedure uses information from the human genome sequence, NCBI gene
annotations, verified eukaryotic promoters (EPD), experimentally proven
binding sites (Transfac) and homologies to mouse and rat (HomGL/HomoloGene).
We test the approach on 18 upstream regions of experimentally verified AP-1 target genes. About a half of the known sites belong to high-scoring candidates. Three top-scoring elements are confirmed by Cluster-Buster and high homologies.
The same analysis we applied to genes found to be up- or downregulated due to mutated RAS. We performed a detailed literature and computational search for promoter regions. Indications of overrepresented Elk-1 and AP-1 motifs are found via a comparison with shuffled sequences. In some promoters consistent predictions of clustered binding sites were obtained.