332 research outputs found

    Bioinformatic Investigations Into the Genetic Architecture of Renal Disorders

    Get PDF
    Modern genomic analysis has a significant bioinformatic component due to the high volume of complex data that is involved. During investigations into the genetic components of two renal diseases, we developed two software tools. // Genome-Wide Association Studies (GWAS) datasets may be genotyped on different microarrays and subject to different annotation, leading to a mosaic case-control cohort that has inherent errors, primarily due to strand mismatching. Our software REMEDY seeks to detect and correct strand designation of input datasets, as well as filtering for common sources of noise such as structural and multi-allelic variants. We performed a GWAS on a large cohort of Steroid-sensitive nephrotic syndrome samples; the mosaic input datasets were pre-processed with REMEDY prior to merging and analysis. Our results show that REMEDY significantly reduced noise in GWAS output results. REMEDY outperforms existing software as it has significantly more features available such as auto-strand designation detection, comprehensive variant filtering and high-speed variant matching to dbSNP. // The second tool supported the analysis of a newly characterised rare renal disorder: Polycystic kidney disease with hyperinsulinemic hypoglycemia (HIPKD). Identification of the underlying genetic cause led to the hypothesis that a change in chromatin looping at a specific locus affected the aetiology of the disease. We developed LOOPER, a software suite capable of predicting chromatin loops from ChIP-Seq data to explore the possible conformations of chromatin architecture in the HIPKD genomic region. LOOPER predicted several interesting functional and structural loops that supported our hypothesis. We then extended LOOPER to visualise ChIA-PET and ChIP-Seq data as a force-directed graph to show experimental structural and functional chromatin interactions. Next, we re-analysed the HIPKD region with LOOPER to show experimentally validated chromatin interactions. We first confirmed our original predicted loops and subsequently discovered that the local genomic region has many more chromatin features than first thought

    Identification of conserved regulatory elements by comparative genome analysis

    Get PDF
    BACKGROUND: For genes that have been successfully delineated within the human genome sequence, most regulatory sequences remain to be elucidated. The annotation and interpretation process requires additional data resources and significant improvements in computational methods for the detection of regulatory regions. One approach of growing popularity is based on the preferential conservation of functional sequences over the course of evolution by selective pressure, termed 'phylogenetic footprinting'. Mutations are more likely to be disruptive if they appear in functional sites, resulting in a measurable difference in evolution rates between functional and non-functional genomic segments. RESULTS: We have devised a flexible suite of methods for the identification and visualization of conserved transcription-factor-binding sites. The system reports those putative transcription-factor-binding sites that are both situated in conserved regions and located as pairs of sites in equivalent positions in alignments between two orthologous sequences. An underlying collection of metazoan transcription-factor-binding profiles was assembled to facilitate the study. This approach results in a significant improvement in the detection of transcription-factor-binding sites because of an increased signal-to-noise ratio, as demonstrated with two sets of promoter sequences. The method is implemented as a graphical web application, ConSite, which is at the disposal of the scientific community at . CONCLUSIONS: Phylogenetic footprinting dramatically improves the predictive selectivity of bioinformatic approaches to the analysis of promoter sequences. ConSite delivers unparalleled performance using a novel database of high-quality binding models for metazoan transcription factors. With a dynamic interface, this bioinformatics tool provides broad access to promoter analysis with phylogenetic footprinting

    Identification of co-regulated candidate genes by promoter analysis.

    Get PDF
    EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    Evaluation of phylogenetic footprint discovery for predicting bacterial cis-regulatory elements and revealing their evolution

    Get PDF
    The detection of conserved motifs in promoters of orthologous genes (phylogenetic footprints) has become a common strategy to predict cis-acting regulatory elements. Several software tools are routinely used to raise hypotheses about regulation. However, these tools are generally used as black boxes, with default parameters. A systematic evaluation of optimal parameters for a footprint discovery strategy can bring a sizeable improvement to the predictions.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Studying the regulatory landscape of flowering plants

    Get PDF
    • …
    corecore