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...ctional TFBS from a spurious site. In the case of multi-species comparison, there is a wide spectrum of partial conservation, which could be effectively used by a program, as shown in earlier studies =-=[68]-=-. We therefore anticipate that our improved evolutionary model and methods will make a crucial difference to the accuracy of multi-species analysis. Our method takes a set of TF motifs as input; howev...

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...ion, as in Figure 1C and D, correct alignment of motifs may even be impossible. Alignment algorithms may also incorrectly align orthologous regulatory regions from higher organisms: Kheradpour et al. =-=(16)-=- have shown examples of Drosophila melanogaster Mef-2 binding sites that are not correctly aligned to the orthologous sites in 11 related Drosophila species. In consequence, motif finding algorithms b...

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... - Published by genome.cshlp.orgDownloaded fromsused to distinguish regulatory motif instances under purifying evolutionary selection that are thus more likely to be associated with functional edges (=-=Kheradpour et al. 2007-=-). Third, D. melanogaster has been the target of several recent studies mapping the in vivo binding of TFs, providing genome-wide target regions for a growing number of TFs (Zeitlinger et al. 2007; Li...

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... promoter elements. Negligible improvement through sequence conservation Functional motifs are generally conserved above average, since mutations that abrogate their function are negatively selected (=-=Kheradpour et al. 2007-=-; Stark et al. 2007; Margulies and Birney 2008; Roy et al. 2010). We tried several versions of alignment-free and alignment-based conservation scores in XXmotif. The alignment-based conservation P-val...

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...n used to assist in the comparative study of regulatory mechanisms across organisms [20–22]. For example, gene-expression data [22], sequence data like transcriptional factor binding site (TFBS) data =-=[20, 21]-=-, and cis-regulatory elements [22] have all been used in this context. Moreover, a broad range of model organisms have been studied, including bacteria [8], yeast [20, 22], and fruit fly [21]. While t...

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...er allows us to do a large-scale discovery of conserved gene clusters with exible evolutionary constraints. We borrowed the notion of branch length score (BLS) from the study of regulatory elements (=-=Kheradpour et al., 2007-=-) to quantify the evolutionary constraint of gene clusters, taking into account the phylogenetic tree structure of species. Our computational approach is applied to more than 100 bacterial genomes. We...

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...r success have included the availability of experimentally characterized motifs [13–14], gene function annotations [9], the opportunity to use alignment-based comparison among closely related species =-=[15]-=- and other sources of information such as chromatin immunoprecipitation-based binding data [16], tissue-specific gene expression data [1,17], etc. However, to a researcher interested in gene regulator...