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At least 955 records · Page 53Linked to original sources
PubMed2006

On the identification of differentially expressed genes: improving the generalized F-statistics for Affymetrix microarray gene expression data.

It has been shown that the generalized F-statistics can give satisfactory performances in identifying differentially expressed genes with microarray data. However, for some complex diseases, it is still possible to identify a high proportion of false positives because of the modest differential expressions of disease related genes and the systematic noises of microarrays. The main purpose of this study is to develop statistical methods for Affymetrix microarray gene expression data so that the impact on false positives from non-expressed genes can be reduced. I proposed two novel generalized F-statistics for identifying differentially expressed genes and a novel approach for estimating adjusting factors. The proposed statistical methods systematically combine filtering of non-expressed genes and identification of differentially expressed genes. For comparison, the discussed statistical methods were applied to an experimental data set for a type 2 diabetes study. In both two- and three-sample analyses, the proposed statistics showed improvement on the control of false positives.

Computer Simulation↗
PubMed2005

Pros and cons in the use of SNPs in forensic kinship investigation: a comparative analysis with STRs.

Recent advances in single nucleotide polymorphisms (SNPs) research have raised the possibility that these markers could replace the forensically established short tandem repeats (STRs). In this work, we compare STRs and SNPs applicability for kinship investigation in terms of expected informative content and probability of occurrence of "difficult cases" (when isolated Mendelian incompatibilities between alleged father and child are found). Since SNPs have a much lower mutation rate than STRs, these difficulties were expected to occur less frequently if SNPs were used instead of STRs. The purpose of this paper is to make some simulations allowing the estimation of how often such difficult cases are expected to occur using both types of markers and how serious can be their impact in routine work. Our results demonstrate that a battery based exclusively on SNPs matching the informative power of current STR kits would be prone, if applied to routine paternity investigation, to the occurrence of cases where the statistical evidence would be inconclusive. We infer that the introduction of a SNP based strategy, as a substitute to the now classical STR approach poses statistical problems that must be carefully evaluated.

Adult↗
PubMedDate not supplied

[How useful is the calculation of total scores for questionnaires concerning health related quality of life?].

Questionnaires for health related quality of life generally comprise several subscales. These subscales can be summarized into a total score. The aim of this article is to test the justification of such an integration from a statistical point of view. By means of a representative sample of the German population (n = 1981) the correlative relationships among six questionnaires are assessed: NHP, EORTC QLQ-C30, HADS, MFI-20, GBB-24 and Whiteley index. The corrrelations between the total scores are markedly higher than the mean correlations among the subscales between the tests. Even in those cases where the subscales share the same subdimension the correlations are not higher than the correlations between these subscales and the (unspecific) total scores. The advantage of sharing a common area is as great as the disadvantage of the lower number of items. By means of the Spearman-Brown formula the relationship between the number of items and the reliability of the scale is discussed in detail. It can be concluded that the calculation of total scores is useful and justified from a statistical perspective.

Algorithms↗
PubMed1995

On likelihood distance for outliers detection.

The likelihood distance has been widely used to detect outlying observations in data analysis. Cook and Weisberg (5) suggested that the likelihood distance may be compared to a chi 2 distribution for large samples. In this paper, we show that use of the chi 2 distribution is inappropriate. The results indicate that the likelihood distance does not follow an asymptotically chi 2 distribution. Instead, it converges to 0 in probability as the sample size increases. We show that for a nondegenerate limiting distribution, a multiplication factor related to the sample size n is needed. In general, the limiting distribution of this modified statistic is model-dependent.

Data Interpretation, Statistical↗
PubMed2006

Thermoluminescence glow curve deconvolution and its statistical analysis using the flexibility of spreadsheet programs.

Analysing thermoluminescence glow curves involves the solving of a system of non-linear equations. These equations are either differential equations that must be solved numerically or functional approximations for their solution. The current paper presents software with the functions needed for the study of glow curves that is not a stand-alone computer program but an extension of MS Excel. It supplies functions that solve the general one trap model for the thermoluminescence process without the use of approximating functions. Combined with the Solver utility of Excel this gives a very flexible system for the analysis of glow curves. Functions for analysing the statistics of the deconvolution results are included.

Algorithms↗
PubMed2002

Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints.

Bisphosphonates are the current standard of palliative care for patients with bone lesions from breast cancer and multiple myeloma. This article discusses the selection of endpoints and statistical methods used to assess clinical efficacy of bisphosphonate therapies in patients with bone metastases. Recent studies of pamidronate and zoledronic acid have set the standards for the design and conduct of multicenter, randomized, placebo-controlled trials to assess the clinical benefit of bisphosphonates in patients with bone metastases. Studies of zoledronic acid have demonstrated objective, significant, and enduring benefits in patients with a broad range of primary cancers, including prostate cancer, using robust clinical endpoints. Other bisphosphonates, including clodronate, have been investigated for the treatment of bone metastases, but these studies have been relatively small. This review first considers issues of trial design and analysis, with particular emphasis on the statistical requirements for the rigorous analysis of multiple events occurring in the same patient, and then reviews the results of bisphosphonate trials in patients with breast or prostate cancers metastatic to bone in the light of these statistical considerations.

Bone Neoplasms↗
PubMedDate not supplied

Bootstrapping of gene-expression data improves and controls the false discovery rate of differentially expressed genes.

The ordinary-, penalized-, and bootstrap t-test, least squares and best linear unbiased prediction were compared for their false discovery rates (FDR), i.e. the fraction of falsely discovered genes, which was empirically estimated in a duplicate of the data set. The bootstrap-t-test yielded up to 80% lower FDRs than the alternative statistics, and its FDR was always as good as or better than any of the alternatives. Generally, the predicted FDR from the bootstrapped P-values agreed well with their empirical estimates, except when the number of mRNA samples is smaller than 16. In a cancer data set, the bootstrap-t-test discovered 200 differentially regulated genes at a FDR of 2.6%, and in a knock-out gene expression experiment 10 genes were discovered at a FDR of 3.2%. It is argued that, in the case of microarray data, control of the FDR takes sufficient account of the multiple testing, whilst being less stringent than Bonferoni-type multiple testing corrections. Extensions of the bootstrap simulations to more complicated test-statistics are discussed.

Analysis of Variance↗
PubMed2006

Analysis of neighborhood dynamics of forest ecosystems using likelihood methods and modeling.

Advances in computing power in the past 20 years have led to a proliferation of spatially explicit, individual-based models of population and ecosystem dynamics. In forest ecosystems, the individual-based models encapsulate an emerging theory of "neighborhood" dynamics, in which fine-scale spatial interactions regulate the demography of component tree species. The spatial distribution of component species, in turn, regulates spatial variation in a whole host of community and ecosystem properties, with subsequent feedbacks on component species. The development of these models has been facilitated by development of new methods of analysis of field data, in which critical demographic rates and ecosystem processes are analyzed in terms of the spatial distributions of neighboring trees and physical environmental factors. The analyses are based on likelihood methods and information theory, and they allow a tight linkage between the models and explicit parameterization of the models from field data. Maximum likelihood methods have a long history of use for point and interval estimation in statistics. In contrast, likelihood principles have only more gradually emerged in ecology as the foundation for an alternative to traditional hypothesis testing. The alternative framework stresses the process of identifying and selecting among competing models, or in the simplest case, among competing point estimates of a parameter of a model. There are four general steps involved in a likelihood analysis: (1) model specification, (2) parameter estimation using maximum likelihood methods, (3) model comparison, and (4) model evaluation. Our goal in this paper is to review recent developments in the use of likelihood methods and modeling for the analysis of neighborhood processes in forest ecosystems. We will focus on a single class of processes, seed dispersal and seedling dispersion, because recent papers provide compelling evidence of the potential power of the approach, and illustrate some of the statistical challenges in applying the methods.

Computer Simulation↗
PubMed2001

[Count on your beliefs. Bayes--not the P value--measures credence].

This article (the second of two) describes traditional (frequentistic) statistical analysis in the context of the confidence interval. Bayesian analysis is described in two settings. In the choice between diagnostic alternatives, the bayesian approach offers useful integration of new information with previous knowledge. With regard to the evaluation of clinical trial data, this article exemplifies bayesian analysis as contrasted with traditional analysis, and advantages of the former are cited. A brief literature review exposes the wide applicability of bayesian analysis in medical statistics.

Bayes Theorem↗
PubMed1991

[The importance of ADP for medical statistics].

Recent german articles concerning medical statistics give priority to data acquisition. This contribution describe the statistical analysis and presentation of the results of the Swiss accident insurance Company (SUVA) with 1.9 million of insured workers. This documentation covers per year approximately 450,000 accidents at work and in free time. The documentation include primarily the insurance-data, for medical purposes we use the adjacent diagnoses (up to 20 per accident). The new medical statistic (SUMEST) begins with the accidents of the year 1984, updated until 1988, this means, that we have a statistic of the outcome of accidents. For the analysis we use properties of the personality, details of what happened, injury, expenses for healing and results. The primary presentation is a collection of tables for every diagnosis (total 417) with the most important criteria for the cases. It is provided to publish results of special problems like time of disability, influence of algodystrophy etc. The possibility to analyse a big documentation (25 MBytes) with a personal computer give to the physician the possibility to perform the statistical analysis himself and to select the significant results immediately.

Data Interpretation, Statistical↗
PubMed1988

Applications of statistical analysis in diagnostic histopathology and cytopathology.

Corresponding to the rapid increase in the amount of data available for use in clinical diagnoses, there is an increased need for procedures that can provide the diagnostician with meaningful statistical summaries of data and with statements concerning the statistical significance associated with a diagnostic evaluation. It has been demonstrated that multivariate statistical assessment of clinical material can provide consistent, reliable and highly sensitive diagnostic clues, even in instances in which trained personnel are unable to see any change. Several examples of applications of statistical analyses in diagnostic cytology and histopathology are given in this paper. The examples were chosen to be illustrative of the different types of problems for which statistical analyses have been found useful. These problems differ with respect to the extent of the statistical methods thus far developed and the difficulty involved in developing further analyses. For many problems, appropriate statistical analyses are readily available; other problems require definition of custom-made test statistics and, in some cases, also definition of new statistical distributions. The problems discussed here are only a small sample of the existing problems, but they provide at least an indication of the scope of the role that statistics plays in cytopathologic and histopathologic diagnosis.

Cytological Techniques↗
PubMed2002

Using standard desk-top tools to monitor medical error rates.

Many experts believe it is time to do something about the high number of medical errors and adverse events highlighted in the recent IOM report. This article examines how front line managers can use a valuable quality improvement/assurance tool--the statistical process control chart--to track and analyze medical error rates. It includes a step-by-step guide to the creation and interpretation of a demonstration chart, discusses potential barriers to the use of statistical process control charts, and suggests ways to overcome those barriers.

Data Collection↗
PubMed2003

Characterization of the double-partitioning modules of R27: correlating plasmid stability with plasmid localization.

Plasmid R27 contains two independent partitioning modules, designated Par1 and Par2, within transfer region 2. Par1 is member of the type I partitioning family (Walker-type ATPase), and Par2 is a member of the type II partitioning family (actin-type ATPase). Stability tests of cloned Par1 and Par2 and insertional disruptions of Par1 and Par2 within R27 demonstrated that Par1 is the major stability determinant whereas Par2 is the minor stability determinant. Creation of double-partitioning mutants resulted in R27 integrating into the chromosome, suggesting that at least one partitioning module is required for R27 to exist in the extrachromosomal form. Using the lacO/LacI-green fluorescent protein (GFP) system, we labeled and visualized R27 and R27 partitioning mutants (Par1(-) and Par2(-)) under different growth conditions in live Escherichia coli cells. Plasmid R27 was visualized as the discrete GFP foci present at the mid- and quarter-cell regions in >99% of the cells. Time lapse experiments demonstrated that an increase in R27 plasmid foci resulted from focus duplication in either the mid- or quarter-cell regions of E. coli. Both R27 Par(-) variants gave a high percentage of plasmidless cells, as suggested by a uniform GFP signal, and cells with GFP patterns scattered throughout the entire cell, suggesting that plasmid molecules are randomly distributed throughout the cytoplasm. Those cells that did contain R27 Par(-) with one or two discrete foci had localization patterns that were statistically different from those formed with wild-type R27. Therefore, these results suggest that partitioning-impaired plasmids are characterized by individual and clustered plasmids that are randomly located within the host cytoplasm.

Adenosine Triphosphatases↗
PubMed1995

Automated short tandem repeat (STR) analysis in forensic casework--a strategy for the future.

Short tandem repeat (STR) loci are routinely analysed for forensic purposes in the UK. Because small regions of DNa are amplified, successful results are more likely to be obtained from highly degraded material where the DNA fragment length may be < 500 bp. The method is superceeding conventional analysis with single locus probes (SLPs). Dimeric STR loci display stutter artefacts, hence STRs used in casework are restricted to tri or tetrameric loci. Some STRs are complex repeats and have more alleles than simple repeats - for example the locus D21S11 has 21 alleles which differ in size by 2 bp because of the presence/absence of a hexanucleotide within the block of tetrameric repeats. These loci are of great potential interest because they combine increased discriminating power with reduced potential to stutter. Multiplexing 4 different loci with different dye labelled primers (i.e. carrying out polymerase chain reaction of 4 loci simultaneously) using the ABD 373A automated sequencer enables a large numbers of samples to be processed. In addition data aquisition and manipulation is automated so that minimum postelectrophoresis operator input is required. It is our aim to develop a system equivalent in power to that of 4 single locus probes. To achieve this we have developed an octoplex system consisting of 7 loci and a sex test (amelogenin locus) which has a probability of chance of association of 10(-9); the power of this system is equivalent to that achieved by 4 conventional SLPs.

Alleles↗
PubMed2006

A systematic comparison of intracellular cyclic AMP and calcium signalling highlights complexities in human VPAC/PAC receptor pharmacology.

VPAC/PAC receptor activation classically results in cyclic-AMP production, with limited reports evaluating calcium signalling. These studies systematically characterise intracellular cyclic-AMP ([cAMP](i)) and calcium ([Ca(2+)](i)) responses in CHO-cells expressing recombinant human (h) VPAC/PAC receptors (hVPAC(1)R, hVPAC(2)R, hPAC(1)R), using two simple, non-radioactive, HT-amenable assays. The rank order of potency (ROP) of the agonists VIP, PACAP-27 and PACAP-38 was similar in both assays for each individual receptor subtype, although potencies (EC(50)) in the [Ca(2+)](i) assay were approximately 100-fold lower. Importantly, this shift was also evident in SHSY-5Y cells endogenously expressing hPAC(1)R. Furthermore, [Ala(11,22,28)]VIP and maxadilan were selective hVPAC(1)R and hPAC(1)R agonists, respectively, and although R3P65 had no demonstrable hVPAC(2)R selectivity, these compounds exhibited comparable reductions in [Ca(2+)](i) EC(50) values. In contrast, PG97-269 and PG99-465, putatively selective hVPAC(1)R and hVPAC(2)R antagonists, respectively, were marginally less potent in [cAMP](i) studies, whereas M65 was equipotent at hPAC(1)R. Moreover, PG99-465 alone increased [cAMP](i) at all three hVPAC/PAC receptor subtypes, with full hVPAC(1)R and hPAC(1)R agonism. With equivalent agonist ROPs generated in both assays, [Ca(2+)](i) signalling provides an alternative approach to examine hVPAC/PAC receptor pharmacology. However, these studies underscore the paucity of receptor selective compounds, complexities in comparing drug potencies across assays, and the pleiotropic nature of VPAC/PAC-receptor signalling.

Amino Acid Sequence↗
PubMed2003

Population genetic structure of the toad Bufo woodhousii: an empirical assessment of the effects of haplotype extinction on nested cladistic analysis.

Nested cladistic analysis (NCA) is increasingly being used to infer historical population-level processes, including population fragmentation, range expansion and long-distance colonization. However, the effects on interpretation of NCA inferences of stochastic extinction of haplotypes due to genetic drift (lineage sorting), or of haplotype loss via localized biotic or climatic influences, have not been thoroughly explored. We provide empirical evidence suggesting that NCA may misinterpret population history when haplotypes or haplotype groups from one clade are replaced by those of another clade. We do so by using NCA to analyse mitochondrial sequences from the toad Bufo woodhousii from 45 locations spanning the Great Plains and southwestern USA. Portions of this region were glaciated and/or desertified in the late Pleistocene and early Holocene, and hence uninhabitable for plains-dwelling organisms. Although NCA inferences of isolation-by-distance and gradual range expansion in B. woodhousii are compatible with expectations based on climatic data and toad biology, NCA also detected several instances of long-distance movement. Such movement seems unlikely, given the low vagility of this species. We conclude that inferences of long-distance colonization likely result from extinction of haplotypes in intervening areas. We suggest using additional methods to look for congruent inferences, and amending the NCA inference key, to help avoid misinterpretations resulting from haplotype extinction.

Animals↗