Biomedical subjects
Publications and source records attributed to Marek Sergot.
SEAN is an application that predicts single nucleotide polymorphisms (SNPs) using multiple sequence alignments produced from expressed sequence tag (EST) clusters. The algorithm uses rules of sequence identity and SNP abundance to determine the quality of the prediction. A Java viewer is provided to display the EST alignments and predicted SNPs.
Whole genome microarrays allow assessment of the profile of genes expressed under particular experimental conditions, including external stimuli such as pH or temperature, and internal changes brought about by deleting or over-expressing a gene. Such experiments produce large data sets, for which sophisticated analysis software is available. What is lacking are tools for analysing data sets from different experiments, in order to test and generate hypotheses about the links between regulatory networks. We describe here a method for presenting results from different experiments as a directed graph constructed using an automated graph drawing program xneato, enhanced by a logic program designed to cluster data and aid in the generation of hypotheses about possible gene interactions. A web-based front-end to the system has been constructed to explore and manipulate the graphical displays produced. Results of microarray experiments on Mycobacterium tuberculosis were used to develop and evaluate the visualization tool and initiate the development of an inference system for gene interactions based on such data. The GeneGraph project can be accessed at: zebrafish.doc.ic.ac.uk
GANESH is a software package designed to support the genetic analysis of regions of human and other genomes. It provides a set of components that may be assembled to construct a self-updating database of DNA sequence, mapping data, and annotations of possible genome features. Once one or more remote sources of data for the target region have been identified, all sequences for that region are downloaded, assimilated, and subjected to a (configurable) set of standard database-searching and genome-analysis packages. The results are stored in compressed form in a relational database, and are updated automatically on a regular schedule so that they are always immediately available in their most up-to-date versions. A Java front-end, executed as a stand alone application or web applet, provides a graphical interface for navigating the database and for viewing the annotations. There are facilities for importing and exporting data in the format of the Distributed Annotation System (DAS), enabling a GANESH database to be used as a component of a DAS configuration. The system has been used to construct databases for about a dozen regions of human chromosomes and for three regions of mouse chromosomes.
A variety of loci with interesting patterns of regulation such as imprinted expression, and critical functions such as involvement in tumour necrosis factor pathways, map to a distal portion of mouse chromosome 12. This region also contains disease related loci including the 'Legs at odd angles' mutation (Loa) that we are pursuing in a positional cloning project. To further define the region and prepare for comparative sequencing projects, we have produced genetic, radiation hybrid, physical and transcript maps of the region, with probes providing anchors between the maps. We show a summary of 95 markers and 91 genomic clones that has enabled us to identify 18 transcripts including new genes and candidates for Loa which will help in future studies of gene context and regulation.