Lipid Metabolism and Comparative Genomics

Unilever asked the Study Group to focus on two problems. The first concerned dysregulated lipid metabolism which is a feature of many diseases including metabolic syndrome, obesity and coronary heart disease. The Study Group was asked to develop a model of the kinetics of lipoprotein metabolism between healthy and obese states incorporating the activities of key enzymes. The second concerned the use of comparative genomics in understanding and comparing metabolic networks in bacterium. Comparative genomics is a method to make inferences on the genome of a new organism using information of a previously charaterised organism. The first mathematical question is how one would quantify such a metabolic map in a statistical sense, in particular, where there are different levels of confidence for presense of different parts of the map. The next and most important question is how one can design a measurement strategy to maximise the confidence in the accuracy of the metabolic map

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Lipid-induced insulin resistance in human skeletal muscle

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Ontology learning with text mining: Two use cases in lipoprotein metabolism and toxicology

Background: The engineering of ontologies, especially with a view to a text-mining use, is still a new research field. There does not yet exist a well-defined theory and technology for ontology construction. Many of the ontology design steps remain manual and are based on personal experience and intuition. However, there exist a few efforts on automatic construction of ontologies in the form of extracted lists of terms and relations between them. Results: We share experience acquired during the manual development of a lipoprotein metabolism ontology (LMO) to be used for text-mining. We compare the manually created ontology terms with the automatically derived terminology from four different automatic term recognition methods. The top 50 predicted terms contain up to 89% relevant terms. For the top 1000 terms the best method still generates 51% relevant terms. In a corpus of 3066 documents 53% of LMO terms are contained and 38% can be generated with one of the methods. Secondly we present a use case for ontology-based search for toxicological methods. Conclusions: Given high precision, automatic methods can help decrease development time and provide significant support for the identification of domain-specific vocabulary. The coverage of the domain vocabulary depends strongly on the underlying documents. Ontology development for text mining should be performed in a semi-automatic way; taking automatic term recognition results as input. Availability: The automatic term recognition method is available as web service, described at http://gopubmed4.biotec.tu- dresden.de/IdavollWebService/services/CandidateTermGeneratorService?wsd

Terminologies for text-mining; an experiment in the lipoprotein metabolism domain-0

In relevant terms within the top retrieved terms. The chart shows the overlap within the top predicted terms with LMO and the manual evaluation (MANUAL). For example, from the top 50 predicted terms by Text2Onto, 20% are in LMO and 36% are correct according to the manual evaluation.<p><b>Copyright information:</b></p><p>Taken from "Terminologies for text-mining; an experiment in the lipoprotein metabolism domain"</p><p>http://www.biomedcentral.com/1471-2105/9/S4/S2</p><p>BMC Bioinformatics 2008;9(Suppl 4):S2-S2.</p><p>Published online 25 Apr 2008</p><p>PMCID:PMC2367629.</p><p></p