computational discovery of regulatory elements in acontinuous expression space计算发现监管元素acontinuous表达空间.pdfVIP

Lajoie et al. Genome Biology 2012, 13:R109 /2012/13/11/R109 METHOD Open Access Computational discovery of regulatory elements in a continuous expression space * Mathieu Lajoie , Olivier Gascuel, Vincent Lefort and Laurent Bréhélin Abstract Approaches for regulatory element discovery from gene expression data usually rely on clustering algorithms to partition the data into clusters of co-expressed genes. Gene regulatory sequences are then mined to find overrepresented motifs in each cluster. However, this ad hoc partition rarely fits the biological reality. We propose a novel method called RED2 that avoids data clustering by estimating motif densities locally around each gene. We show that RED2 detects numerous motifs not detected by clustering-based approaches, and that most of these correspond to characterized motifs. RED2 can be accessed online through a user-friendly interface. Keywords: motif discovery, gene regulation, co-expressed genes, clustering, k-nearest neighbors Background agent of human malaria - whose A+T content reaches Gene expression is modulated depending on time, space almost 90% in intergenic regions [8]. and environmental conditions. This process involves Second, clustering assumes that: (i) a natural partition many levels, including chromatin structure, transcrip- of the genes in well-defined clusters exists and can be tion, transcript stability or localization, and translation. inferred from the data, and (ii) co-regulated gene sets At most of these levels, regulation is achieved through are disjoint. In fact, determining the real number of the binding of regulatory proteins with