Abstract
BackgroundGenome layout and gene regulation appear to be interdependent. Understanding this interdependence is key to exploring the dynamic nature of chromosome conformation and to engineering functional genomes. Evidence for non-random genome layout, defined as the relative positioning of either co-functional or co-regulated genes, stems from two main approaches. Firstly, the analysis of contiguous genome segments across species, has highlighted the conservation of gene arrangement (synteny) along chromosomal regions. Secondly, the study of long-range interactions along a chromosome has emphasised regularities in the positioning of microbial genes that are co-regulated, co-expressed or evolutionarily correlated. While one-dimensional pattern analysis is a mature field, it is often powerless on biological datasets which tend to be incomplete, and partly incorrect. Moreover, there is a lack of comprehensive, user-friendly tools to systematically analyse, visualise, integrate and exploit regularities along genomes.ResultsHere we present the Genome REgulatory and Architecture Tools SCAN (GREAT:SCAN) software for the systematic study of the interplay between genome layout and gene expression regulation. GREAT:SCAN is a collection of related and interconnected applications currently able to perform systematic analyses of genome regularities as well as to improve transcription factor binding sites (TFBS) and gene regulatory network predictions based on gene positional information.ConclusionsWe demonstrate the capabilities of these tools by studying on one hand the regular patterns of genome layout in the major regulons of the bacterium Escherichia coli. On the other hand, we demonstrate the capabilities to improve TFBS prediction in microbes. Finally, we highlight, by visualisation of multivariate techniques, the interplay between position and sequence information for effective transcription regulation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1047-0) contains supplementary material, which is available to authorized users.
Highlights
Genome layout and gene regulation appear to be interdependent
Genome REgulatory and Architecture Tools SCAN (GREAT):SCAN is available in two versions: a) running as an online application integrated in the computational framework of the GREAT portal in the servers of abSYNTH platform; b) as a downloadable stand-alone command line Docker image of each individual tool, to facilitate incorporation into pipelines
We demonstrate the analytical capabilities of GREAT:SCAN:PATTERNS: by conducting a complete analysis of the seven major E. coli regulons, report results of regions of periodic arrangement which are associated with large scale genomic structures such as the organisation in macro-domains [23] and discuss preliminary results on the use of GREAT:SCAN:PRECISION to formulate and test biological hypotheses
Summary
Genome layout and gene regulation appear to be interdependent. Understanding this interdependence is key to exploring the dynamic nature of chromosome conformation and to engineering functional genomes. Evidence for non-random genome layout, defined as the relative positioning of either co-functional or co-regulated genes, stems from two main approaches. We developed GREAT:SCAN (Genome REgulatory Architecture Tools:SCAN), a collection of on-line software tools designed to perform systematic detection of regular patterns along genomes, integrate and interconnect results between available methods and provide informative visualisations. GREAT:SCAN extends two algorithms previously developed by our team for the detection of periodically arranged genes [12] and the prediction of transcription factor binding sites (TFBS) [13] It provides a web user interface which streamlines the usage of these algorithms, performs a fully automated analysis of regularities among genomic features, extends with novel functionalities the analytical capabilities of the previous software and reports results in human- (plots and graphs) as well as in machine- (tables) readable formats. GREAT:SCAN is available in two versions: a) running as an online application integrated in the computational framework of the GREAT portal in the servers of abSYNTH platform (absynth.issb.genopole. fr/Bioinformatics/tools/GREAT); b) as a downloadable stand-alone command line Docker image of each individual tool, to facilitate incorporation into pipelines
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