bookmark Motif-PIE An approach to understand interactions between TFs. Motif-PIE has been tested using Saccharomyces cerevisiae as a model system. Instead of gene expression profiles, we focus on the sequence motifs in the upstream promoters. The strength of this algorithm lies in the fact that it is sequence-based; it can be applied to genes without expression data or previously determined binding motifs. By taking groups of genes whose upstream sequences are known to be bound by two TFs, we made ab initio predictions of their corresponding TF binding sites and examined the relationship between these two sites on the promoter sequences. The sequence relationships between the binding motifs were examined in terms of preferences in distance and orientation, reflecting possible spatial relationships between TFs. We further analyzed these predicted relationships using gene expression data and found that they are dynamic and condition-dependent.