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An Alignment-free Method for Detection of Functional Conservation of Regulatory Sequences

Cis-regulatory modules (CRMs) can drive precise spatio-temporal gene expression patterns. Some recent studies show that CRMs may function similarly despite substantial sequence divergence. This implies that firstly alignment-based sequence comparison tools are not applicable for further decoding such CRMs and secondly that some of the CRMs must share common patterns that drive almost identical regulatory outputs but possibly with different arrangements of binding sites. Here, we present our Regulatory Region Scoring (RRS) method which is based on potential distribution of transcription factors. Comparing two regulatory sequences for (dis)similarity has important applications such as: 1. Detect functionally conserved enhancer regions in orthologous genomes even if the enhancer regions do not align.