A mixture model-based approach to the clustering of microarray expression data

Motivation: This paper introduces the software EMMIX-GENE that has been developed for the specific purpose of a model-based approach to the clustering of microarray expression data, in particular, of tissue samples on a very large number of genes. The latter is a nonstandard problem in parametric cluster analysis because the dimension of the feature space (the number of genes) is typically much greater than the number of tissues. A feasible approach is provided by first selecting a subset of the genes relevant for the clustering of the tissue samples by fitting mixtures of t distributions to rank the genes in order of increasing size of the likelihood ratio statistic for the test of one versus two components in the mixture model. The imposition of a threshold on the likelihood ratio statistic used in conjunction with a threshold on the size of a cluster allows the selection of a relevant set of genes. However, even this reduced set of genes will usually be too large for a normal mixture model to be fitted directly to the tissues, and so the use of mixtures of factor analyzers is exploited to reduce effectively the dimension of the feature space of genes. Results: The usefulness of the EMMIX-GENE approach for the clustering of tissue samples is demonstrated on two well-known data sets on colon and leukaemia tissues. For both data sets, relevant subsets of the genes are able to be selected that reveal interesting clusterings of the tissues that are either consistent with the external classification of the tissues or with background and biological knowledge of these sets.

Estimating Two-Stage Models for Genetic Influences on Alcohol, Tobacco or Drug Use Initiation and Dependence Vulnerability in Twin and Family Data

Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions., recovery of simulated genetic and environmental correlations becomes possible, Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.

Epizootic activity of Murray Valley encephalitis virus in an aboriginal community in the southeast Kimberley region of western Australia: Results of cross-sectional and longitudinal serologic studies

Murray Valley encephalitis (MVE) virus is a mosquito-borne flavivirus causing severe encephalitis with a resultant high morbidity and mortality. In the period 1989-1993. we undertook a cross-sectional and longitudinal studs by annually screening members of a small remote Aboriginal community in northwestern Australia for MVE virus antibodies. Of the estimated 250-300 people in the community. 249 were tested, and 52.6% had positive serology to MVE. The proportion testing positive increased with increasing age group. and males were slightly more likely to be positive than females. During the study period. a high proportion of the population seroconverted to MVE: the clinical/subclinical ratio seems to be lower than previously reported. Although MVE is mostly asymptomatic, the devastating consequences of clinical illness indicate that advice should be provided regarding the avoidance of mosquito bites. Our longitudinal study showed that the risk of seroconversion was similar for each age group. not just the young.

Testicular myxosporidiasis in anurans, with a description of Myxobolus fallax n. sp.

During studies of amphibian sperm cryopreservation, a new species of myxosporidean parasite (Myxozoa, Myxosporae) was observed in the testes of the Australian dwarf green tree frog Litoria fallax (Peters). Myxosporidiasis was found to have no affect on L. fallax body condition or sperm numbers. Myxobolus spores from L. fallax are morphologically distinct from Myxobolus hylae spores (infecting the sympatric Litoria aurea Lesson) and the three previously named (exotic to Australia) Myxobolus species found in anurans. Myxobolus fallax n. sp. is characterised by: pseudocyst white, spherical to ovoid, 141 x74 to 438 x337 mum in diameter (mature); plasmodium with spores loosely arranged within interior. Spores ovoid 13.4 +/- 0.5 (12.6-14.6) mum length, 9.5 +/- 0.4 (8.3-10.6) mum width, 6.8 +/- 0.4 (6.5-7.6) mum depth, 1.4 +/- 0.1 (1.3-1.6) length/width; polar capsules broadly pyriform and equal in size 4.2 +/- 0.3 (3.3-4.7) mum length, 2.4 +/- 0.2 (2.1-2.8) mum width; filament coils 7-8, wound tightly and perpendicular to the longitudinal axis of the capsule; polar filament 34 +/- 7.0 (18-50) mum length; intercapsular appendix and sutural ridge folds absent; and iodinophilous vacuole and mucous envelope lacking. In addition to this new species, data from archival samples of M. hylae are provided which show two morphologically distinct spore types. Both appeared rarely in the same pseudocysts and we cautiously retain the single species.

Testing insect movement theory: empirical analysis of pest data routinely collected from agricultural crops

Observations of an insect's movement lead to theory on the insect's flight behaviour and the role of movement in the species' population dynamics. This theory leads to predictions of the way the population changes in time under different conditions. If a hypothesis on movement predicts a specific change in the population, then the hypothesis can be tested against observations of population change. Routine pest monitoring of agricultural crops provides a convenient source of data for studying movement into a region and among fields within a region. Examples of the use of statistical and computational methods for testing hypotheses with such data are presented. The types of questions that can be addressed with these methods and the limitations of pest monitoring data when used for this purpose are discussed. (C) 2002 Elsevier Science B.V. All rights reserved.

Development of a fully quantitative approach to the interpretation of stress echocardiography using radial and longitudinal myocardial velocities

Background: Tissue Doppler may be used to quantify regional left ventricular function but is limited by segmental variation of longitudinal velocity from base to apex and free to septal walls. We sought to overcome this by developing a composite of longitudinal and radial velocities. Methods and Results. We examined 82 unselected patients undergoing a standard dobutamine echocardiogram. Longitudinal velocity was obtained in the basal and mid segments of each wall using tissue Doppler in the apical views. Radial velocities were derived in the same segments using an automated border detection system and centerline method with regional chords grouped according to segment location and temporally averaged. In 25 patients at low probability of coronary disease, the pattern of regional variation in longitudinal velocity (higher in the septum) was the opposite of radial velocity (higher in the free wall) and the combination was homogenous. In 57 patients undergoing angiography, velocity in abnormal segments was less than normal segments using longitudinal (6.0 +/- 3.6 vs 9.0 +/- 2.2 cm/s, P = .01) and radial velocity (6.0 +/- 4.0 vs 8.0 +/- 3.9 cm/s, P = .02). However, the composite velocity permitted better separation of abnormal and normal segments (13.3 +/- 5.6 vs 17.5 +/- 4.2 cm/s, P = .001). There was no significant difference between the accuracy of this quantitative approach and expert visual wall motion analysis (81% vs 84%, P = .56). Conclusion: Regional variation of uni-dimensional myocardial velocities necessitates site-specific normal ranges, probably because of different fiber directions. Combined analysis of longitudinal and radial velocities allows the derivation of a composite velocity, which is homogenous in all segments and may allow better separation of normal and abnormal myocardium.

Who does not gain weight? Prevalence and predictors of weight maintenance in young women

OBJECTIVE: To investigate the prevalence and predictors of weight maintenance over time in a large sample of young Australian women. DESIGN: This population study examined baseline and 4y follow-up data from the cohort of young women participating in the Australian Longitudinal Study on Women's Health. SUBJECTS: A total of 8726 young women aged 18 - 23y at baseline. MEASURES: Height, weight and body mass index (BMI); physical activity; time spent sitting; selected eating behaviours (eg dieting, disordered eating, takeaway food consumption); cigarette smoking, alcohol consumption; parity; and socio-demographic characteristics. RESULTS: Only 44% of the women reported their BMI at follow-up to be within 5% of their baseline BMI (maintainers); 41% had gained weight and 15% had lost weight. Weight maintainers were more likely to be in managerial or professional occupations; to have never married; to be currently studying; and not to be mothers. Controlling for sociodemographic factors, weight maintainers were more likely to be in a healthy weight range at baseline, and to report that they spent less time sitting, and consumed less takeaway food, than women who gained weight. CONCLUSIONS: Fewer than half the young women in this community sample maintained their weight over this 4y period in their early twenties. Findings of widespread weight gain, particularly among those already overweight, suggest that early adulthood, which is a time of significant life changes for many women, may be an important time for implementing strategies to promote maintenance of healthy weight. Strategies which encourage decreased sitting time and less takeaway food consumption may be effective for encouraging weight maintenance at this life stage.

Phase equilibrium data and liquidus for the system "MnO"-CaO-(Al2O3+SiO2) at Al2O3/SiO2 of 0.41

Phase-equilibrium data and the liquidus for the system. "MnO"-CaO-(Al2O3-SiO2) at a manganese-rich alloy saturation have been determined in the temperature range from 1423 to 1723 K. The results are presented in the form of a pseudoternary section "MnO"-CaO-(Al2O3 + SiO2) with an Al2O3/SiO2 weight ratio of 0.41. The following primary phases are present in the range of conditions investigated:, 3Al(2)O(3).2SiO(2); SiO2; MnO.Al2O3-2SiO(2); (Mn,Ca)O.SiO2; 2(Mn,Ca)O.SiO2; MnO.Al2O3; (Mn,Ca)O; alpha-2CaO.SiO2; alpha'-2CaO.SiO2; 2CaO.Al2O3.SiO2; CaO.SiO2, and CaO.Al2O3.2SiO(2). The presence of alumina in this system is shown to have a significant effect on the liquidus compared to the system "MnO"-CaO-SiO2, leading to, the stabilization of the anorthite and gehlenite phases.

Mineral chemistry, whole-rock compositions, and petrogenesis of leg 176 gabbros: Data and discussion

We report mineral chemistry, whole-rock major element compositions, and trace element analyses on Hole 735B samples drilled and selected during Leg 176. We discuss these data, together with Leg 176 shipboard data and Leg 118 sample data from the literature, in terms of primary igneous petrogenesis. Despite mineral compositional variation in a given sample, major constituent minerals in Hole 735B gabbroic rocks display good chemical equilibrium as shown by significant correlations among Mg# (= Mg/[Mg+Fe2+]) of olivine, clinopyroxene, and orthopyroxene and An (=Ca/[Ca+Na]) of plagioclase. This indicates that the mineral assemblages olivine + plagioclase in troctolite, plagioclase + clinopyroxene in gabbro, plagioclases + clinopyroxene + olivine in olivine gabbro, and plagioclase + clinopyroxene + olivine + orthopyroxene in gabbronorite, and so on, have all coprecipitated from their respective parental melts. Fe-Ti oxides (ilmenite and titanomagnetite), which are ubiquitous in most of these rocks, are not in chemical equilibrium with olivine, clinopyroxene, and plagioclase, but precipitated later at lower temperatures. Disseminated oxides in some samples may have precipitated from trapped Fe-Ti–rich melts. Oxides that concentrate along shear bands/zones may mark zones of melt coalescence/transport expelled from the cumulate sequence as a result of compaction or filter pressing. Bulk Hole 735B is of cumulate composition. The most primitive olivine, with Fo = 0.842, in Hole 735B suggests that the most primitive melt parental to Hole 735B lithologies must have Mg# ≤ 0.637, which is significantly less than Mg# = 0.714 of bulk Hole 735B.