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PubMed1990

Origin of tetrapods inferred from their mitochondrial DNA affiliation to lungfish.

This paper shows that questions of an unexpected phylogenetic depth can be addressed by the study of mitochondrial DNA (mtDNA) sequences. For decades, it has been unclear whether coelacanth fishes or lungfishes are the closest living relatives of land vertebrates (Tetrapoda). Segments of mtDNA from a lungfish, the coelacanth, and a ray-finned fish were sequenced and compared to the published sequence of a frog mtDNA. A tree based on inferred amino acid replacements, silent transversions, and ribosomal RNA (rRNA) substitutions showed with statistical confidence that the lungfish mtDNA is more closely related to that of the frog than is the mtDNA of the coelacanth. This result appears to rule out the possibility that the coelacanth lineage gave rise to land vertebrates; hence, morphological characters that link the latter two groups are possibly due to convergent evolution or reversals and not to common descent. Besides supporting the theory that land vertebrates arose from an offshoot of the lineage leading to lungfishes, the molecular tree facilitates an evolutionary interpretation of the morphological differences among the living forms. It would appear that the common ancestor of lungfishes and tetrapods already possessed multiple morphological traits preadapting their locomotion, circulation, and respiration for life on land.

Animals↗
PubMed2005

A local-scale in situ approach for stressor identification of biologically impaired aquatic systems.

We propose a formal causal evaluation inference process that uses a local-scale in situ approach and provides statistically defensible correlative conclusions for the biological impairment in 303(d)-listed water bodies. Fish assemblage, water chemistry, and aquatic habitat data from 66 locations in the Limberlost watershed, Indiana, were collected in August 2003 to evaluate the condition of the watershed. Anthropogenic stressors were identified from a numerical classification analysis of fish assemblage data using a biological integrity response gradient. Physical and chemical stressors were evaluated relative to the biological integrity response gradient using the Kruskal Wallis analysis of variance by ranks test. Three water chemistry variables (sodium, chloride, and barium) were associated with biological integrity. The percent run habitat, channel morphology score, and Qualitative Habitat Evaluation Index score varied with the degree of dredging. We observed a negative response between the number of species and the biological integrity gradient and a positive response with the percent tolerant individuals. This local-scale in situ approach to physical and chemical data analysis, combined with concurrent biological data collection, provided correlative relations to the impaired condition with localized environmental stressors.

Animals↗
PubMed2005

Assessment of soil erodibility indices for conservation reserve program lands in southwestern Kansas using satellite imagery and GIS techniques.

The soil erodibility index (EI) of Conservation Reserve Program (CRP) lands, which was the major criterion for CRP enrollment, was assessed for six counties in southwestern Kansas using USGS seamless digital elevation model data and Geographical Informational System techniques. The proportion of land areas with EI values of 8 or lower was less than 1% of the entire study area and most of the land areas (72.5%) were concentrated on EI values between 8 and 24. Although land acreage with EI values of 24 or higher decreased dramatically, the proportion of CRP lands to the other land-use types did not change much from low to high EI levels. The soil EI and physical soil characteristics of the CRP lands were compared to those of other land-use types. In general, the mean EI values of the land-use types were strongly correlated with physical soil properties, including organic matter content, clay content, available water capacity, permeability, and texture. CRP lands were compared in detail with cropland in terms of their soil characteristics to infer the pivotal cause of the land transformation. Although there was no significant statistical difference in EI between cropland and CRP soils, soil texture, soil family, and permeability were statistically different between the two. Statistical analyses of these three variables showed that CRP soils had coarser texture and higher permeability on average than cropland soils, indicating that CRP lands in the study area are drier than cropland soils. Therefore, soil moisture characteristics, not necessarily soil erosion potential, might have been the key factor for CRP enrollment in the study area.

Agriculture↗
PubMed2004

High throughput multiple combination extraction from large scale polymorphism data by exact tree method.

Single nucleotide polymorphisms (SNPs) are increasingly becoming important in clinical settings as useful genetic markers. For the evaluation of genetic risk factors of multifactorial diseases, it is not sufficient to focus on individual SNPs. It is preferable to evaluate combinations of multiple markers, because it allows us to examine the interactions between multiple factors. If all the combinations possible were evaluated round-robin, the number of calculations would rapidly explode as the number of markers analyzed increased. To overcome this limitation, we devised the exact tree method based on decision tree analysis and applied it to 14 SNP data from 68 Japanese stroke patients and 189 healthy controls. From the obtained tree models, we succeeded in extracting multiple statistically significant combinations that elevate the risk of stroke. From this result, we inferred that this method would work more efficiently in the whole genome study, which handles thousands of genetic markers. This exploratory data mining method will facilitate the extraction of combinations from large-scale genetic data and provide a good foothold for further verificatory research.

Adult↗
PubMed1990

A genetic map of human chromosome 17p.

A genetic linkage map was constructed with 18 loci from the short arm and pericentric region of chromosome 17 typed on the CEPH reference families. The genetic map includes three markers extracted from the CEPH public database. Nine loci could be ordered using a threshold of odds of at least 1000:1 against alternative orders during the map construction process. With a reduced tolerance of 100:1, a total of 13 loci could be placed on the map spanning a distance of approximately 60 cM in females and 46 cM in males. There were statistically significant differences between the male and the female genetic maps. The order inferred from the genetic data was consistent with the physical localizations of these probes obtained from somatic cell hybrids and tumor deletion studies. This map should be useful for genetic fine mapping of 17p loci.

Alleles↗
PubMed2006

Using Bayesian statistics to estimate the coefficients of a two- component second-order chlorine bulk decay model for a water distribution system.

Most chlorine decay models for the bulk phase in a water distribution system consider only chlorine concentration and time. Clark [1998. Chlorine demand and trihalomethane formation kinetics: a second-order model. J. Environ. Eng. 124(1), 16-24] first proposed a two-component second-order chlorine decay model based on the concept of competing reacting substances. A corrected mathematical formulation is developed and, because the recent findings suggested that not all natural organic matter (NOM) is involved in the chlorine decay process, an additional parameter is introduced. A parameter assignment method employing Bayesian statistical analysis incorporating Monte Carlo Markov chain (MCMC) with Gibbs sampling to make inferences, is employed in the estimation of model parameters. Three parameters are estimated for the model, namely the ratio of chlorine to TOC, the chlorine reaction rate, and a fraction factor of TOC which represents the true amount of TOC involved in chlorine decay process. Water samples taken from Goderich in the summer of 2005, are used for estimating the parameters.

Bayes Theorem↗
PubMed2001

Bayesian restoration of ion channel records using hidden Markov models.

Hidden Markov models have been used to restore recorded signals of single ion channels buried in background noise. Parameter estimation and signal restoration are usually carried out through likelihood maximization by using variants of the Baum-Welch forward-backward procedures. This paper presents an alternative approach for dealing with this inferential task. The inferences are made by using a combination of the framework provided by Bayesian statistics and numerical methods based on Markov chain Monte Carlo stochastic simulation. The reliability of this approach is tested by using synthetic signals of known characteristics. The expectations of the model parameters estimated here are close to those calculated using the Baum-Welch algorithm, but the present methods also yield estimates of their errors. Comparisons of the results of the Bayesian Markov Chain Monte Carlo approach with those obtained by filtering and thresholding demonstrate clearly the superiority of the new methods.

Bayes Theorem↗
PubMed1998

Meta-analysis of anterior veneer restorations in clinical studies.

OBJECTIVES: To make an inventory of clinical studies on veneer restorations (VRs) using a meta-analysis review procedure and to aggregate an overall survival result for four types of VRs. METHODS: From the dental literature published from 1983 to November 1996, papers were selected using an in- and exclusion protocol in a two-step procedure. Additionally, the papers selected were subjected to a quality assessment. Although not all studies used an identical definition of 'failure of a restoration', this item was chosen to be the common study outcome. After a homogeneity test, cumulative survival curves were constructed by pooling the data from the studies. RESULTS: On a 0-1 scale, the weighted overall mean quality score of the studies was 0.57 (s.e. 0.09). There was adequate agreement between the independent assessors. The results of the quality assessment could not be used as weights for the survivals, but the quality outcome supports the description of the sample of studies. From the nine studies on porcelain VRs, the pooled cumulative proportion of survival after 3 years was 0.92 (s.e. 0.01) and from three studies on preformed acrylic VRs this figure was 0.74 (s.e. 0.03). From both direct and indirect resin composite VRs, data from only one study were available after 2.5 and 2 years, respectively. CONCLUSION: The evaluative and statistical basis of clinical VR studies may be improved to obtain an effective inference of the results. Furthermore, porcelain VRs show acceptable longevity after 3 years, which appears to be better than that of preformed acrylic VRs.

Acrylic Resins↗
PubMed2003

Statistical testing and null distributions: what to do when samples are not random.

Selected literature related to statistical testing is reviewed to compare the theoretical models underlying parametric and nonparametric inference. Specifically, we show that these models evaluate different hypotheses, are based on different concepts of probability and resultant null distributions, and support different substantive conclusions. We suggest that cognitive scientists should be aware of both models, thus providing them with a better appreciation of the implications and consequences of their choices among potential methods of analysis. This is especially true when it is recognized that most cognitive science research employs design features that do not justify parametric procedures, but that do support nonparametric methods of analysis, particularly those based on the method of permutation/randomization.

Humans↗
PubMed1999

Systematic determination of genetic network architecture.

Technologies to measure whole-genome mRNA abundances and methods to organize and display such data are emerging as valuable tools for systems-level exploration of transcriptional regulatory networks. For instance, it has been shown that mRNA data from 118 genes, measured at several time points in the developing hindbrain of mice, can be hierarchically clustered into various patterns (or 'waves') whose members tend to participate in common processes. We have previously shown that hierarchical clustering can group together genes whose cis-regulatory elements are bound by the same proteins in vivo. Hierarchical clustering has also been used to organize genes into hierarchical dendograms on the basis of their expression across multiple growth conditions. The application of Fourier analysis to synchronized yeast mRNA expression data has identified cell-cycle periodic genes, many of which have expected cis-regulatory elements. Here we apply a systematic set of statistical algorithms, based on whole-genome mRNA data, partitional clustering and motif discovery, to identify transcriptional regulatory sub-networks in yeast-without any a priori knowledge of their structure or any assumptions about their dynamics. This approach uncovered new regulons (sets of co-regulated genes) and their putative cis-regulatory elements. We used statistical characterization of known regulons and motifs to derive criteria by which we infer the biological significance of newly discovered regulons and motifs. Our approach holds promise for the rapid elucidation of genetic network architecture in sequenced organisms in which little biology is known.

Animals↗
PubMed2006

A tumor progression model for hepatocellular carcinoma: bioinformatic analysis of genomic data.

BACKGROUND & AIMS: It is widely recognized that genomic abnormalities underpin the development of human cancers. Aberrant patterns of chromosomal changes may represent useful information that can be used in classifying the complex traits of liver cancer cases for the genetic events involved in tumor carcinogenesis, tumor progression, and prognosis. METHODS: Genome-wide chromosomal aberrations of 158 hepatitis B virus-associated hepatocellular carcinoma (HCC) were studied by comparative genomic hybridization (CGH). By application of a self-organizing tree algorithm, statistically significant CGH events were used to construct an evolutionary tree that could infer patient subgroups with different degrees of tumor progression. The key CGH events in the subgroups were identified. The clinical significance of the groupings and the key CGH events were examined. RESULTS: Based on the patterns of significant chromosomal aberrations derived, 3 HCC subgroups organized in an evolutionary tree were identified. The groupings possessed information reflecting the degrees of tumor progression, including numbers of chromosomal aberrations, tumor stages, tumor sizes, and disease outcome. Gains of 1q21-23 and 8q22-24 were identified as genomic events associated with the early development of HCC. Gain of 3q22-24, however, was identified as 1 of the late genomic events found to be associated with tumor recurrence and poor overall patient survival. CONCLUSIONS: A tumor progression model for HCC was constructed and revealed chromosomal imbalances that were significantly associated with clinical pathologic characteristics of the disease. This model explains a significant part of the variations in clinical outcome among HCC patients.

Adult↗
PubMed1990

Estimation of genetic correlation: interpretation of experiments using selectively bred and inbred animals.

There is increasing interest in determining the extent to which multiple characters related to drug sensitivity are influenced by common genes. The principal method for testing for the existence of such genetic correlations has been examination of pairs of mouse or rat lines selectively bred for sensitivity or resistance to a single behavioral effect of a drug. When a pair of selected lines is found to differ significantly on some trait other than the one on which they were selected, it is commonly concluded that significant genetic correlation between the traits exists, implying the action of a common set of genes on the two responses. In addition, results from comparisons of lines of animals selected for trait X and tested for trait Y may be compared with results from lines selected for trait Y and tested for trait X. As the number of correlated responses in selected lines increases, it becomes more important to adhere to sensible, consensual guidelines for interpreting such line differences. The principles underlying phenotypic and genotypic correlational analyses with selected lines are discussed. A scheme is presented to allow standardization across laboratories of inferences about the relative strength of genetic association from experiments with selected lines. Statistical and practical experimental issues are addressed. Estimates of genetic correlations may also be derived from the correlation of mean trait values across a panel of inbred strains. Existing data have sometimes found estimates of genetic correlations made with one approach to be inconsistent with those estimated in other ways. Possible reasons for this are discussed. Finally, the relationship between phenotypic correlations and genetic correlations is discussed. Phenotypic and genetic correlations for a pair of traits may differ widely, and may even be opposite in sign. Both are characteristic of the population from which they are sampled. Phenotypic correlations estimated within selected lines may change over time, as the additive genetic variance in the selected trait is exhausted. A specific example of this phenomenon is given.

Alcoholic Intoxication↗
PubMed2005

Adaptive design and estimation in randomized clinical trials with correlated observations.

Clinical trial designs involving correlated data often arise in biomedical research. The intracluster correlation needs to be taken into account to ensure the validity of sample size and power calculations. In contrast to the fixed-sample designs, we propose a flexible trial design with adaptive monitoring and inference procedures. The total sample size is not predetermined, but adaptively re-estimated using observed data via a systematic mechanism. The final inference is based on a weighted average of the block-wise test statistics using generalized estimating equations, where the weight for each block depends on cumulated data from the ongoing trial. When there are no significant treatment effects, the devised stopping rule allows for early termination of the trial and acceptance of the null hypothesis. The proposed design updates information regarding both the effect size and within-cluster correlation based on the cumulated data in order to achieve a desired power. Estimation of the parameter of interest and its confidence interval are proposed. We conduct simulation studies to examine the operating characteristics and illustrate the proposed method with an example.

Biometry↗
PubMed2006

Comment on "Evidence for positive epistasis in HIV-1".

Bonhoeffer et al. (Reports, 26 November 2004, p. 1547) presented evidence for positive epistasis in a clinical data set of HIV-1 mutants and corresponding fitness values. We demonstrate that biases in the original and simulated data sets may lead to erroneous evidence for epistasis. More rigorous statistical tests must be used to account for such biases before one can infer epistasis.

Anti-HIV Agents↗
PubMed1994

Is ambient ethene a cancer risk factor?

Ethene is, on a molar basis, a major urban air pollutant. It has been shown beyond doubt that a fraction of inhaled ethene is metabolized in mammals (including humans) via ethylene oxide, an electrophilic reagent that has been shown to be mutagenic and carcinogenic. To the extent that the linearity hypothesis for dose-response relationships at low levels is accepted, exposure to ethene is therefore expected to lead to a risk increment. In order to judge whether ethene as a single compound should be considered a risk factor, it has to be evaluated whether this risk increment is negligibly small or of concern to individuals or societies. The magnitude of the cancer risk from ethene cannot be inferred from animal experiments. Because of saturation of the metabolism of ethene, sufficient statistical power cannot be attained in long-term animal tests with about 100 animals per dose. By application of the radiation-dose equivalent of the unit of target dose of ethylene oxide and using the best (although still uncertain) value for the conversion factor (about 5%), exposure to 10 ppb ethene--a level occurring in urban areas--is expected to lead to a lifetime risk of cancer death amounting to approximately 70 per 100,000. According to a recent estimate the average exposure in Sweden to ethene is some six times lower. These figures are uncertain by a factor of at least three. They indicate ethene to be a risk factor of concern.

Air Pollutants↗
PubMed2006

Geographic analysis of host use, development, and habitat use of an acanthocephalan species, Leptorhynchoides thecatus.

Leptorhynchoides thecatus (Linton, 1891), an acanthocephalan parasite of freshwater fishes, varies in host use, development, and habitat use throughout North America. Spatial structure of these characteristics was examined from data extracted from the literature. Geographic patterns were inferred from point comparisons using correllograms and then tested with Moran's I statistic for global and local significance, and visually from regional means within major river drainages. Species of Micropterus Lacepède, 1802 (black basses) were common hosts in most regions, except the Lower Mississippi and South Atlantic regions where species of Lepomis Rafinesque, 1819 (sunfishes) were common hosts. Development, described as the proportions of adults relative to cystacanths (extraintestinal juveniles), decreased with latitude. Habitat use of L. thecatus showed marked geographic patterns. Leptorhynchoides thecatus occurred in the intestine of sunfishes in the South Atlantic and Lower Mississippi regions, in the ceca in fish of all species included in the study in the Missouri and Texas-Gulf regions, and both in ceca and intestines in fish of all species in northern regions. Leptorhynchoides thecatus showed geographic patterning within the variable traits across the range of the species. These patterns may be the result of ecological factors or of genetic differences that might indicate L. thecatus comprises multiple cryptic species.

Acanthocephala↗
PubMed2006

Combining multistate capture-recapture data with tag recoveries to estimate demographic parameters.

Matrix population models that allow an animal to occupy more than one state over time are important tools for population and evolutionary ecologists. Definition of state can vary, including location for metapopulation models and breeding state for life history models. For populations whose members can be marked and subsequently reencountered, multistate mark-recapture models are available to estimate the survival and transition probabilities needed to construct population models. Multistate models have proved extremely useful in this context, but they often require a substantial amount of data and restrict estimation of transition probabilities to those areas or states subjected to formal sampling effort. At the same time, for many species, there are considerable tag recovery data provided by the public that could be modeled in order to increase precision and to extend inference to a greater number of areas or states. Here we present a statistical model for combining multistate capture-recapture data (e.g., from a breeding ground study) with multistate tag recovery data (e.g., from wintering grounds). We use this method to analyze data from a study of Canada Geese (Branta canadensis) in the Atlantic Flyway of North America. Our analysis produced marginal improvement in precision, due to relatively few recoveries, but we demonstrate how precision could be further improved with increases in the probability that a retrieved tag is reported.

Animal Migration↗
PubMed2006

Low-order conditional independence graphs for inferring genetic networks.

As a powerful tool for analyzing full conditional (in-)dependencies between random variables, graphical models have become increasingly popular to infer genetic networks based on gene expression data. However, full (unconstrained) conditional relationships between random variables can be only estimated accurately if the number of observations is relatively large in comparison to the number of variables, which is usually not fulfilled for high-throughput genomic data. Recently, simplified graphical modeling approaches have been proposed to determine dependencies between gene expression profiles. For sparse graphical models such as genetic networks, it is assumed that the zero- and first-order conditional independencies still reflect reasonably well the full conditional independence structure between variables. Moreover, low-order conditional independencies have the advantage that they can be accurately estimated even when having only a small number of observations. Therefore, using only zero- and first-order conditional dependencies to infer the complete graphical model can be very useful. Here, we analyze the statistical and probabilistic properties of these low-order conditional independence graphs (called 0-1 graphs). We find that for faithful graphical models, the 0-1 graph contains at least all edges of the full conditional independence graph (concentration graph). For simple structures such as Markov trees, the 0-1 graph even coincides with the concentration graph. Furthermore, we present some asymptotic results and we demonstrate in a simulation study that despite their simplicity, 0-1 graphs are generally good estimators of sparse graphical models. Finally, the biological relevance of some applications is summarized.

Algorithms↗