Issue No. 04 - July-Aug. (2014 vol. 11)
Matteo Comin , Dept. of Inf. Eng., Univ. of Padova, Padua, Italy
Davide Verzotto , Dept. of Comput. & Syst. Biol., Genome Inst. of Singapore, Singapore, Singapore
The cell-type diversity is to a large degree driven by transcription regulation, i.e., enhancers. It has been recently shown that in high-level eukaryotes enhancers rarely work alone, instead they collaborate by forming clusters of cis-regulatory modules (CRMs). Even if the binding of transcription factors is sequence-specific, the identification of functionally similar enhancers is very difficult. A similarity measure to detect related regulatory sequences is crucial to understand functional correlation between two enhancers. This will allow large-scale analyses, clustering and genome-wide classifications. In this paper we present Under2, a parameter-free alignment-free statistic based on variable-length words. As opposed to traditional alignment-free methods, which are based on fixed-length patterns or, in other words, tied to a fixed resolution, our statistic is built upon variable-length words, and thus multiple resolutions are allowed. This will capture the great variability of lengths of CRMs. We evaluate several alignment-free statistics on simulated data and real ChIP-seq sequences. The new statistic is highly successful in discriminating functionally related enhancers and, in almost all experiments, it outperforms fixed-resolution methods. Finally, experiments on mouse enhancers show that Under2 can separate enhancers active in different tissues. Availability: http://www.dei.unipd.it/~ciompin/main/UnderIICRMS.html.
Bioinformatics, Genomics, Customer relationship management, Computational modeling, Computational biology,regulatory sequences comparison, Alignment-free statistics, pattern discovery
Matteo Comin, Davide Verzotto, "Beyond Fixed-Resolution Alignment-Free Measures for Mammalian Enhancers Sequence Comparison", IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol. 11, no. , pp. 628-637, July-Aug. 2014, doi:10.1109/TCBB.2014.2306830