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Beyond Fixed-Resolution Alignment-Free Measures for Mammalian Enhancers Sequence Comparison.
Artigo em Inglês | MEDLINE | ID: mdl-26356333
UNLABELLED: 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:





Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Elementos Facilitadores Genéticos / Análise de Sequência de DNA / Genômica / Mamíferos Limite: Animais / Humanos Idioma: Inglês Revista: ACM Trans Comput Biol Bioinform Assunto da revista: Biologia / Informática Médica Ano de publicação: 2014 Tipo de documento: Artigo