Office of Technology Transfer – University of Michigan

Topo-EP

Technology #5489

High affinity gene enhancers predicted by newly developed algorithm An enhancer prediction software, TOPO-EP, was developed to predict high affinity gene enhancers. In silico methods have frequently been used to identify gene enhancers in Drosophila. However, these methods can be costly and time consuming. An algorithm that predicts sites enriched in transcription factor binding sites was developed that can narrow in on sites that are highly likely to be gene enhancers. Once potential sites are determined, functional testing can validate gene enhancer activity. This gene enhancer predictor algorithm can save researchers lots of time and money by first narrowing in on likely enhancers in their experimental system.

TOPO-EP enhancer prediction software enables identification of gene enhancers The TOPO-EP enhancer prediction software works off a highly modified version of SCORE (Site Clustering Over Random Expectation). Affinity of transcription factor enriched sites on randomly generated chromosomes is determined and pooled to create a robust background model for comparison to real chromosomes. Functional testing in Drosophila of predicted sites indicated that TOPO-EP can identify Hedgehog-responsive enhancers about 25% of the time. This TOPO-EP enhancer prediction software could then be used to further identify enhancers in Drosophila that are highly conserved in mammals. Determination of enhancers in mammalians could be extremely useful in the study of cancer genetics as well as normal gene function. The TOPO-EP software is an invaluable tool for academic and industry-related researchers that are interested in gene regulation and function in healthy and disease states. While similar algorithms, like SCORE, can identify enhancers, they fail to generate a robust background model to minimize noise in the algorithm. SCORE searches for DNA sites highly enriched in transcription factor binding sites, while TOPO-EP takes this idea a few steps further and considers affinity, background sequences, and CTCF boundary sites. TOPO-EP opens a new age of DNA analysis, allowing for improved gene enhancer identification.

Applications • Prediction of gene enhancers in Drosophila • Potential for prediction of gene enhancers in metazoans

Advantages • Robust background model for improved DNA sequence/enhancer analysis • Considers CTCF boundary sites (usually found between promoters and enhancers) • Functional testing reveals a 25% success rate at least in Hedgehog-responsive sites in Drosophila