On the use and abuse of statistical significance.
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Clinical Trials as Topic↗
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Results for “Data Interpretation, Statistical”
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EEG background activity described by a large computerized database.
OBJECTIVE: To show how our newly developed software for classification and storage of visually routinely assessed EEGs are used to evaluate the general background activity (GBA) and the alpha rhythm (AR) in a large number of prospective EEGs. METHODS: EEGs from 4651 consecutive patients were visually assessed using a computerized description system connected to an EEG database. The AR and the GBA apart from the AR were described separately for frequency and amplitude. RESULTS: AR frequencies declined from the age of 45 years and slowed with increasing age independently of non-AR pathology and gender. Females had higher AR frequencies than males. EEGs with non-GBA pathology had lower GBA frequencies and higher GBA amplitudes. Higher GBA amplitudes were associated with lower GBA frequencies in normal EEGs for all age groups. EEG interpretations by 4 independent electroencephalographers showed the same trends, but differed in exact assessment of frequencies and amplitudes. CONCLUSIONS: EEG interpretations stored in a categorized database with easy access to data have successfully been used to evaluate interobserver variation and other quality control measurements. Statistical analysis of the data has at the same time produced new information regarding the development of AR and GBA throughout life.
Adolescent↗
Bias estimation in method comparison studies.
A test and a reference analytical method are usually compared for agreement based on paired data obtained from several independent subjects. Bias between two methods can be classified as constant and proportional. In this article, we provide an approach for maximum likelihood estimation of total bias between two methods and partitioning it into constant and proportional bias for each subject. Normal, binomial, or Poisson distribution are the conditional distributions of the response variable that we have considered here, whereas subjects are considered to be random sample from a normally distributed population. Real data on blood cell counts and hemoglobin are used for demonstration. The estimate of biases can be used to test different statistical hypotheses and/or for graphical interpretation of the agreement. The partitioning of total biases in terms of constant and proportional gives an insight on the sources of disagreement between two methods and helps designers and manufacturer's define a remedial strategy.
Algorithms↗
Statistical methods for repeated qualitative assessments on scales.
Assessments of auditory communication are commonly performed with questionnaires or multi-item instruments. The item responses generate ordered categorical data. The aim of the work reported here was to present a statistical approach that takes account of the non-metric properties of data from rating scales for description of multi-item assessments and for evaluation of change in a study concerning the function of and satisfaction with hearing aids. A small data set from an ongoing study at the Ahlsén Research Institute, Orebro University Hospital was used in the worked examples. The use of individual and median group profiles provided an interpretable description of the data. By means of the ranking approach, which ties the ranks to the pairs of data, the systematic group change in hearing function was evaluated separately from the additional individual changes. The use and misuse of parametric statistical methods on ordered categorical data are also discussed.
Data Interpretation, Statistical↗
Statistics from the inside. 5. Data structures.
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Analysis of Variance↗
Sequence features that correlate with MHC restriction.
Identification of common sequence motifs in antigenic peptides restricted to a specific class II molecule has not been easy due to the large variation in length and sequence that is observed in these peptides. The goal of this study is to develop an automated computerized method for the identification of sequence features and structural determinants that play a role in the MHC restriction of helper T-cell antigenic peptides. For this, we compiled an extended database of helper T-cell sites, including the information on MHC restriction, when available. Two groups of peptides are assigned to each MHC type: (1) peptides that bind to that MHC molecule to elicit a T-cell response, and (2) peptides that were shown experimentally either not to bind to or not to elicit a T-cell proliferative response in association with that MHC molecule. We search for common motifs in the group of binding peptides, and identify significant motifs that are frequent among these peptides but almost absent in the group of non-binding peptides. A motif consists of physical-chemical and structural properties that may be responsible for binding specificity and can be extracted from sequence data, such as, hydrophobicity, charge, hydrogen bonding capability, etc. The first search is performed on the non-aligned binding peptides. Next, the sequences are aligned according to an identified motif and a search for additional, conserved, properties is performed. The statistical significance of the motifs is evaluated as well as their compatibility with published experimental results on substitution effects. Here we demonstrate the general scheme of the analysis and results for I-Ek and I-Ak associated peptides.
Amino Acid Sequence↗
Basic concepts in statistics for veterinary ophthalmologists.
Abstract This review article provides a comprehensive coverage of basic statistical procedures commonly used in biologic experiments and is intended to be a basic guide to the selection of appropriate tests and also to aid the reader in the evaluation of published studies. The focus is on the use, interpretation and presentation of the main statistical tests and their key concepts for the practicing veterinary ophthalmologist. Several examples derived from actual ophthalmic research are presented in the text. Lastly, the article discusses computer-based statistical analysis, provides a list of different software available and gives a practical example of a 'real life' statistical analysis.
Animals↗
A statistical approach for array CGH data analysis.
BACKGROUND: Microarray-CGH experiments are used to detect and map chromosomal imbalances, by hybridizing targets of genomic DNA from a test and a reference sample to sequences immobilized on a slide. These probes are genomic DNA sequences (BACs) that are mapped on the genome. The signal has a spatial coherence that can be handled by specific statistical tools. Segmentation methods seem to be a natural framework for this purpose. A CGH profile can be viewed as a succession of segments that represent homogeneous regions in the genome whose BACs share the same relative copy number on average. We model a CGH profile by a random Gaussian process whose distribution parameters are affected by abrupt changes at unknown coordinates. Two major problems arise: to determine which parameters are affected by the abrupt changes (the mean and the variance, or the mean only), and the selection of the number of segments in the profile. RESULTS: We demonstrate that existing methods for estimating the number of segments are not well adapted in the case of array CGH data, and we propose an adaptive criterion that detects previously mapped chromosomal aberrations. The performances of this method are discussed based on simulations and publicly available data sets. Then we discuss the choice of modeling for array CGH data and show that the model with a homogeneous variance is adapted to this context. CONCLUSIONS: Array CGH data analysis is an emerging field that needs appropriate statistical tools. Process segmentation and model selection provide a theoretical framework that allows precise biological interpretations. Adaptive methods for model selection give promising results concerning the estimation of the number of altered regions on the genome.
Algorithms↗
Iterative character weighting based on mutation frequency: a new method for constructing phyletic trees.
In this paper we present an iterative character weighting method for the construction of phyletic trees. An initial tree is used to calculate the character weights, which are the number of mutations normalized so that the possible range is corrected for. The weights obtained are used to adjust the tree; this process is iterated until a stable tree is found. Using data generated according to a model tree, we show that the trees constructed by the iterative character weighting method converge to the true underlying tree. Using biological data, the trees become closer to the systematic classification of the species concerned, and patterns conflicting with the phylogenetic pattern can be singled out. The method involves a combination of minimal length methods and similarity methods, whereby the strict parsimony criterion is relaxed.
Animals↗
Neutron scattering in the plane of membranes: structure of alamethicin pores.
A technique of neutron in-plane scattering for studying the structures of peptide pores in membranes is described. Alamethicin in the inserted state was prepared and undeuterated and deuterated dilauroyl phosphatidylcholine (DLPC) hydrated with D2O or H2O. Neutron in-plane scattering showed a strong dependence on deuteration, clearly indicating that water is a part of the high-order structure of inserted alamethicin. The data are consistent with the simple barrel-stave model originally proposed by Baumann and Mueller. The theoretical curves computed with this model at four different deuteration conditions agree with the data in all cases. Both the diameter of the water pore and the effective outside diameter of the channel are determined accurately. Alamethicin forms pores in a narrow range of size. In a given sample condition, > 70% of the peptide forms pores of n and n +/- 1 monomers. The pore size varies with hydration and with lipid. In DLPC, the pores are made of n = 8-9 monomers, with a water pore approximately 18 A in diameter and with an effective outside diameter of approximately 40 A. In diphytanoyl phosphatidylcholine, the pores are made of n approximately 11 monomers, with a water pore approximately 26 A in diameter, with an effective outside diameter of approximately 50 A.
Alamethicin↗
Biostatistical consultation for dental research.
Dental science researchers do not really need a detailed, ready-at-hand knowledge of statistics to design and perform high quality scientific research. Although the acquisition and utilization of such knowledge by dental researchers is not discouraged, it is proposed that it is more important for dental researchers to be committed to developing and maintaining a long term, ongoing, interactive consulting relationship with a biostatistician. The nature of this relationship will depend in large part on the complexity of the dental research being conducted. While the statistical consultant will assist in interpreting analytic results for the dental researcher, the latter will need to provide extensive input in assisting in the estimation of sample size and power, and for expressing scientific hypotheses in statistical terms so that the appropriate data analytic methodology can be specified.
Analysis of Variance↗
Separating historic events from recurrent processes in cryptic species: phylogeography of mud snails (Hydrobia spp.).
The present study combines methods that were designed to infer intraspecific relationships (e.g. nested-clade analysis (NCA), mismatch distributions and maximum likelihood gene flow analysis) to analyse historic events and recurrent processes in the cryptic mud snail species Hydrobia acuta and H. glyca. Specifically, we test the proposed allopatry of cryptic species and whether the peculiar range-subdivision of the putative subspecies H. a. acuta and H. a. neglecta is a result of long-distance dispersal or continuous range expansion. The NCA indicates a past fragmentation of the two H. acuta subspecies as well as past fragmentations within H. glyca. Gene-flow analyses show extensive gene flow in an E-W direction (towards the Atlantic) in the Mediterranean H. a. acuta, generally low gene flow in a W-E direction in the Atlantic H. a. neglecta and complex gene-flow pattern in a N-S but also in a S-N direction (against the Gulf Stream) in H. glyca. Based on these data and supportive ecological and oceanographical data, we hypothesize that the separation of the two H. acuta subspecies was not caused by long-distance dispersal but by a range shift and/or range expansion of the closely related competitor H. glyca as a result of an interglacial warming with a subsequent range shift in H. acuta. Moreover, our data do not show evidence for a long-term, stable sympatry of Hydrobia species, supporting the concept of allopatric relationships within cryptic radiations. NCA and gene-flow analyses indicate that the only sympatric population found in our study is the result of a recent dispersal event from the nearby Mediterranean. It is assumed that allopatric relationships in ephemeral Hydrobia populations constitute an evolutionary advantage relative to competition, recruitment and re-establishment of habitats. Mechanisms that could be of relevance for maintaining allopatry are discussed.
Animals↗
Association of serum low-density lipoprotein metabolism with oestrogen receptor gene polymorphisms in healthy children.
The aim of this study was to reveal the association of serum lipid and apolipoprotein levels with oestrogen receptor (ER) Xba I and Pvu II polymorphisms in 102 healthy Japanese school children (56M, 46F) aged 10-15 y. Each genotype of the genomic DNA extracted from peripheral leukocytes was determined using polymerase chain reaction and digestion with Xba I or Pvu II. The genotypes were coded as either X1 or X2 (Xba I) and P1 or P2 (Pvu II), when XI, P1 signified the absence of and X2, P2 the presence of restriction sites. The fasting serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride and apolipoproteins A1, B and E were measured. In the Xba I polymorphism, LDL cholesterol, apolipoprotein B levels of the XI/XI genotype were significantly higher than those of the others. The other lipid and apolipoprotein levels were not significantly different among the three genotypes. In the Pvu II polymorphism, there were no significant differences in serum lipids and lipoproteins among the three genotypes. This study reveals that Xba I polymorphisms are related to LDL metabolism. These findings support previous reports that the LDL-lowering effects of oestrogen occur through the ER (alpha) pathway. The Xba I polymorphism may be one of the genetic factors in the control of LDL metabolism.
Adolescent↗
METIS: multiple extraction techniques for informative sentences.
SUMMARY: METIS is a web-based integrated annotation tool. From single query sequences, the PRECIS component allows users to generate structured protein family reports from sets of related Swiss-Prot entries. These reports may then be augmented with pertinent sentences extracted from online biomedical literature via support vector machine and rule-based sentence classification systems. AVAILABILITY: http://umber.sbs.man.ac.uk/dbbrowser/metis/
Algorithms↗
Partial nucleotide sequence of the pts operon in Salmonella typhimurium: comparative analyses in five bacterial genera.
The nucleotide sequence of a Salmonella typhimurium DNA segment of 549 base pairs which encompasses the operator-promoter of the pts operon, the entirety of the ptsH gene, encoding HPr of the phosphotransferase system (PTS), the first 29 nucleotides of the ptsI gene, encoding Enzyme I of the PTS, and the intercistronic region between the ptsH and ptsI genes was determined and compared with the corresponding sequence from Escherichia coli (De Reuse et al., 1985). The two sequences showed 91% overall identity, with some regions showing sequence conservation and others exhibiting relative divergence. Two open reading frames were identified in both species: one encoded HPr on the 'sense' strand (255 nucleotides; 12 nucleotide differences, no amino acid differences); the other, on the anti-sense strand, consisted of 291 nucleotides (13 nucleotide differences, 13 amino acid differences). While HPr bears a net negative charge, the putative protein encoded by the open reading frame on the anti-sense strand is strongly basic. Computer analyses of HPr proteins from five different bacterial genera revealed four regions which show strong sequence identity and therefore are presumed to be critical for maintenance of biological activity. Two of these regions were specific to Gram-positive bacteria. Proposed functions for each of these regions are discussed. Relative evolutionary distances between the HPr proteins were also computed.
Amino Acid Sequence↗
Molecular determinants of ginkgolide binding in the glycine receptor pore.
Ginkgolides are potent blockers of the glycine receptor Cl- channel (GlyR) pore. We sought to identify their binding sites by comparing the effects of ginkgolides A, B and C and bilobalide on alpha1, alpha2, alpha1beta and alpha2beta GlyRs. Bilobalide sensitivity was drastically reduced by incorporation of the beta subunit. In contrast, the sensitivities to ginkgolides B and C were enhanced by beta subunit expression. However, ginkgolide A sensitivity was increased in the alpha2beta GlyR relative to the alpha2 GlyR but not in the alpha1beta GlyR relative to the alpha1 GlyR. We hypothesised that the subunit-specific differences were mediated by residue differences at the second transmembrane domain 2' and 6' pore-lining positions. The increased ginkgolide A sensitivity of the alpha2beta GlyR was transferred to the alpha1beta GlyR by the G2'A (alpha1 to alpha2 subunit) substitution. In addition, the alpha1 subunit T6'F mutation abolished inhibition by all ginkgolides. As the ginkgolides share closely related structures, their molecular interactions with pore-lining residues were amenable to mutant cycle analysis. This identified an interaction between the variable R2 position of the ginkgolides and the 2' residues of both alpha1 and beta subunits. These findings provide strong evidence for ginkgolides binding at the 2' pore-lining position.
Amino Acid Sequence↗
The use of statistical methodology for the analysis of QA data.
Modern statistical methods offer the quality assurance professional a powerful set of tools for the analysis of health care data. By using well-established procedures the quality assurance professional can isolate and quantify the relative degree of problems, determine statistical significance, and allocate resources towards problem resolution. This article briefly covers the concepts of hypothesis testing and statistical significance and their role in assisting the health care professional to assign priorities for use in problem resolution. Several statistical tests are described in the context of health care data analysis. The distinction between parametric, and non-parametric tests is made and a set of guidelines included on when and where the respective tests should be applied. An outline for the application of these statistical tests to several example situations is presented. Some details of population identification, sampling, and data organization are covered. Interpretation of results in the context of different problem situations is also covered.
Data Collection↗
Tandem repeat deletion in the alpha C protein of group B streptococcus is recA independent.
Group B streptococci (GBS) contain a family of protective surface proteins characterized by variable numbers of repeating units within the proteins. The prototype alpha C protein of GBS from the type Ia/C strain A909 contains a series of nine identical 246-bp tandem repeat units. We have previously shown that deletions in the tandem repeat region of the alpha C protein affect both the immunogenicity and protective efficacy of the protein in animal models, and these deletions may serve as a virulence mechanism in GBS. The molecular mechanism of tandem repeat deletion is unknown. To determine whether RecA-mediated homologous recombination is involved in this process, we identified, cloned, and sequenced the recA gene homologue from GBS. A strain of GBS with recA deleted, A909DeltarecA, was constructed by insertional inactivation in the recA locus. A909DeltarecA demonstrated significant sensitivity to UV light, and the 50% lethal dose of the mutant strain in a mouse intraperitoneal model of sepsis was 20-fold higher than that of the parent strain. The spontaneous rate of tandem repeat deletion in the alpha C protein in vitro, as well as in our mouse model of immune infection, was studied using A909DeltarecA. We report that tandem repeat deletion in the alpha C protein does occur in the absence of a functional recA gene both in vitro and in vivo, indicating that tandem repeat deletion in GBS occurs by a recA-independent recombinatorial pathway.
Animals↗