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Biomedical subjects

A Clare

Publications and source records attributed to A Clare.

At least 19 recordsLinked to original sources
PubMed2006

Functional bioinformatics for Arabidopsis thaliana.

MOTIVATION: The genome of Arabidopsis thaliana, which has the best understood plant genome, still has approximately one-third of its genes with no functional annotation at all from either MIPS or TAIR. We have applied our Data Mining Prediction (DMP) method to the problem of predicting the functional classes of these protein sequences. This method is based on using a hybrid machine-learning/data-mining method to identify patterns in the bioinformatic data about sequences that are predictive of function. We use data about sequence, predicted secondary structure, predicted structural domain, InterPro patterns, sequence similarity profile and expressions data. RESULTS: We predicted the functional class of a high percentage of the Arabidopsis genes with currently unknown function. These predictions are interpretable and have good test accuracies. We describe in detail seven of the rules produced.

Algorithms↗
PubMed2003

Predicting gene function in Saccharomyces cerevisiae.

MOTIVATION: S.cerevisiae is one of the most important model organisms, and has has been the focus of over a century of study. In spite of these efforts, 40% of its open reading frames (ORFs) remain classified as having unknown function (MIPS: Munich Information Center for Protein Sequences). We wished to make predictions for the function of these ORFs using data mining, as we have previously successfully done for the genomes of M.tuberculosis and E.coli. Applying this approach to the larger and eukaryotic S.cerevisiae genome involves modifying the machine learning and data mining algorithms, as this is a larger organism with more data available, and a more challenging functional classification. RESULTS: Novel extensions to the machine learning and data mining algorithms have been devised in order to deal with the challenges. Accurate rules have been learned and predictions have been made for many of the ORFs whose function is currently unknown. The rules are informative, agree with known biology and allow for scientific discovery. AVAILABILITY: All predictions are freely available from http://www.genepredictions.org, all datasets used in this study are freely available from http://www.aber.ac.uk/compsci/Research/bio/dss/yeastdataand software for relational data mining is available from http://www.aber.ac.uk/compsci/Research/bio/dss/polyfarm.

Chromosome Mapping↗
PubMed2001

The utility of different representations of protein sequence for predicting functional class.

MOTIVATION: Data Mining Prediction (DMP) is a novel approach to predicting protein functional class from sequence. DMP works even in the absence of a homologous protein of known function. We investigate the utility of different ways of representing protein sequence in DMP (residue frequencies, phylogeny, predicted structure) using the Escherichia coli genome as a model. RESULTS: Using the different representations DMP learnt prediction rules that were more accurate than default at every level of function using every type of representation. The most effective way to represent sequence was using phylogeny (75% accuracy and 13% coverage of unassigned ORFs at the most general level of function: 69% accuracy and 7% coverage at the most detailed). We tested different methods for combining predictions from the different types of representation. These improved both the accuracy and coverage of predictions, e.g. 40% of all unassigned ORFs could be predicted at an estimated accuracy of 60% and 5% of unassigned ORFs could be predicted at an estimated accuracy of 86%.

Bacterial Proteins↗
PubMed2000

Accurate prediction of protein functional class from sequence in the Mycobacterium tuberculosis and Escherichia coli genomes using data mining.

The analysis of genomics data needs to become as automated as its generation. Here we present a novel data-mining approach to predicting protein functional class from sequence. This method is based on a combination of inductive logic programming clustering and rule learning. We demonstrate the effectiveness of this approach on the M. tuberculosis and E. coli genomes, and identify biologically interpretable rules which predict protein functional class from information only available from the sequence. These rules predict 65% of the ORFs with no assigned function in M. tuberculosis and 24% of those in E. coli, with an estimated accuracy of 60-80% (depending on the level of functional assignment). The rules are founded on a combination of detection of remote homology, convergent evolution and horizontal gene transfer. We identify rules that predict protein functional class even in the absence of detectable sequence or structural homology. These rules give insight into the evolutionary history of M. tuberculosis and E. coli.

Amino Acid Sequence↗
PubMed1995

Evidence for the involvement of cyclic AMP in the pheromonal modulation of barnacle settlement

The involvement of cyclic AMP in the settlement of the cypris larva of Balanus amphitrite amphitrite Darwin has been examined through the use of compounds that affect intracellular cyclic AMP levels. The activation of adenylate cyclase with forskolin, and the inhibition of phosphodiesterase with 3-isobutyl-1-methylxanthine, caffeine and theophylline, significantly increased the settlement of cyprids. Although the analogue dibutyryl cyclic AMP appeared to increase settlement, the effect was not significant. No marked increase in settlement resulted from the incubation of cyprids with dibutyryl cyclic GMP, 8-(4-chlorophenylthio) (CPT) cyclic AMP or papaverine (a phosphodiesterase inhibitor). Miconazole nitrate, an adenylate cyclase inhibitor, prevented settlement, but this effect appeared to be physico-chemical rather than pharmacological. Radioimmunoassay did not clearly show whether cyclic AMP levels changed following exposure of cyprids to a pulse of crude barnacle extract. However, exposure to forskolin significantly increased the cyclic AMP titre of cyprids. We conclude that compounds that alter intracellular cyclic AMP levels alter normal patterns of cyprid settlement. Whether this is because of an alteration in signal transduction is unclear.

Journal Article↗
PubMed1994

Selective serotonin reuptake inhibitors: meta-analysis of discontinuation rates.

A meta-analysis was carried out of 42 published randomized controlled studies comparing the selective serotonin reuptake inhibitors (SSRIs) with the tricyclic antidepressants (TCAs) that measured discontinuation rates for side effects and lack of efficacy by treatment group in order to compare the discontinuation rates for side effects and lack of efficacy. These discontinuation rates were pooled to produce the main outcome measure. Seven studies were placebo controlled and the discontinuation rates in these studies were also pooled in a separate analysis. Significantly fewer patients receiving SSRIs discontinued treatment because of side effects (14.9%) compared with those receiving TCAs (19%) (p < 0.01). There was also a significant difference in discontinuation rates due to side effects in the placebo- and TCA-controlled studies analysed separately, SSRIs (19%) compared with TCAs (27%) (p < 0.01). In both analyses a similar proportion of patients discontinued for lack of efficacy on SSRIs and TCAs. There is a significant and clinically important advantage for the SSRIs compared with the TCAs in the acceptability of treatment measured by the number of discontinuations due to side effects reported in published studies. The risk-benefit calculation favours the SSRIs since there were similar levels of efficacy but more discontinuations with the TCAs. The selection of an antidepressant for first-line treatment requires critical evaluation of the full risk-benefit equation.

Antidepressive Agents, Tricyclic↗
PubMed1992

A triaxial classification of health problems presenting in primary health care. A World Health Organization multi-centre study.

Over the past two decades, research in a variety of countries and settings has revealed the extent to which psychological morbidity and social problems constitute an important proportion of primary health care contacts, either in their own right or in association with physical ill-health. The development of appropriate responses, medical and non-medical, to such problems is, in part, hindered by the relatively low level of awareness concerning the significance of such problems and by currently inappropriate methods of describing and classifying health care problems in the primary care setting. There is a pressing need for an appropriate, relatively simple and flexible classification or list of problems presenting in primary care. This study describes the development, under WHO auspices and in an international setting, of a triaxial classification of health problems and the testing and modification of the classification by means of an international case vignette rating exercise. A psychological problem list and a social problem list, together with detailed glossaries, suitably modified in the light of experience derived from the study, are described, and proposals enumerated of possible ways in which these lists might be further developed and used in research and clinical undertakings in primary care.

Cross-Cultural Comparison↗
PubMed1991

Behavioural psychotherapy in the treatment of irritable bowel syndrome.

The irritable bowel syndrome is a highly prevalent condition whose underlying aetiology is not understood. While many patients respond to a combination of gastrointestinal antispasmodics, bulking agents and dietary manipulation, controlled clinical trials have suggested that the benefit is only marginal and is due mainly to the large placebo effect found in this condition, which has been calculated to range between 54 and 81%. Associations between the syndrome and psychological and social stresses suggest, however, that treatment involving a systematic approach to the management of symptoms may hold out real therapeutic possibilities. In the current study, 42 IBS patients were randomly allocated to either medical treatment or to behavioural psychotherapy with a nurse therapist. They were assessed initially and at 4 and 9 months. There was a general improvement over the 9 months on a number of physical and psychological symptoms measured. However, no differences were found between treatment groups except for changes in two avoidance scores. A significant correlation was found, however, between improvement in the bowel symptoms of IBS (stomach pain and diarrhoea) and improvement in the psychological symptoms measured by the Clinical Interview Schedule, suggesting a close interrelationship between the two.

Adult↗
PubMed1988

A follow-up study on alcoholics with and without co-existing affective disorder.

Three-hundred male alcoholics were selected from consecutive admissions to hospital. They were divided into three diagnostic sub-groups: primary alcoholics; alcoholics with unipolar affective disorder; and alcoholics with bipolar affective disorder. After three follow-up interviews over a 2-year period after hospital discharge, the three sub-groups reported differences in frequency of mood change, amount of treatment received, and hospital attendance, although there were no clear-cut differences in items associated with their alcoholism. There were, however, some indications that bipolar patients functioned at a better level during the follow-up period, particularly those who were older, had a previous history of longer periods of abstinence, and maintained more frequent contact with Alcoholics Anonymous (AA) and their family doctor.

Adolescent↗
PubMed1983

A comparison of alcoholics with and without coexisting affective disorder.

Three hundred male Irish alcoholics were selected from 508 consecutive alcoholic admissions to hospital. Using well defined diagnostic criteria, they were divided into three subgroups (1) primary alcoholics, (2) alcoholics with secondary affective disorder and (3) those with primary affective disorder and secondary alcoholism. Although the three groups reported differences in past history and family history of affective disorder and in time spent in hospital for both alcoholism and affective disorder, there was little to distinguish them in behaviour associated with alcoholism or in family history of alcoholism. The implications of these findings and their significance for the relationship of affective disorder and alcoholism are discussed.

Adolescent↗