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Results for “Bootstrap resampling”

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PubMed2003

Cloning, sequencing and phylogenetic/phenetic classification of an estrogen receptor alpha (alpha) subtype of sheepshead minnow (Cyprinodon variegatus).

The estrogen receptor (ER) is a key component of the reproductive system of both teleosts and tetrapods. In this study, the sequence and evolutionary relationship of sheepshead minnow (Cyprinodon variegatus) ER were examined. Total RNA from livers of adult laboratory-reared gravid female C. variegatus was reverse-transcribed to prepare cDNA. Nested pairs of gene-specific degenerative primers derived from conserved amino acid sequences of the ER DNA binding domain were used to amplify an internal fragment of the ER cDNA of C. variegatus using polymerase chain reaction (PCR) followed by rapid amplification of cDNA ends (RACE). The amplified cDNA products were inserted into pGEM T-Easy Vector for cloning and sequencing. The cloned ER cDNA segments gave a 524-amino-acid ER sequence, which represents approximately 80% of the sequence. The use of PHYLIP for phylogenetic analysis with the maximum parsimony method and for phenetic analysis with the neighbor-joining method, along with bootstrap resampling, using 24 known sequences of alpha and beta ER subtypes (both teleosts and tetrapods) indicated that the ER cDNA sequence of C. variegatus has strong homology to the alpha-subtype (ER alpha) of other teleostean fish, especially the closely related killifish species, Japanese medaka (Oryzias latipes). Because ER alpha was the only subtype found, it appears that the alpha-subtype is predominant in C. variegatus liver.

Amino Acid Sequence↗

PubMed1998

An approximate bootstrap technique for variance estimation in parametric images.

Parametric imaging procedures offer the possibility of comprehensive assessment of tissue metabolic activity. Estimating variances of these images is important for the development of inference tools in a diagnostic setting. However, these are not readily obtained because the complexity of the radio-tracer models used in the generation of a parametric image makes analytic variance expressions intractable. On the other hand, a natural extension of the usual bootstrap resampling approach is infeasible because of the expanded computational effort. This paper suggests a computationally practical, approximate simulation strategy to variance estimation. Results of experiments done to evaluate the approach in a simplified model one-dimensional problem are very encouraging. Diagnostic checks performed on a single real-life positron emission tomography (PET) image to test for the feasibility of applying the procedure in a real-world PET setting also show some promise. The suggested methodology is evaluated here in the context of parametric images extracted by mixture analysis; however, the approach is general enough to extend to other parametric imaging methods.

Algorithms↗

PubMed2006

In vivo quantification of serotonin transporters using [(11)C]DASB and positron emission tomography in humans: modeling considerations.

Positron emission tomography (PET) studies of the serotonin transporter (5-HTT) in the human brain are increasingly using the radioligand [(11)C]N, N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine. A variety of models have been applied to such data in several published articles; however to date, these models have not been validated with test-retest data. We recruited 11 healthy subjects and conducted two identical scans on each subject on the same day. We considered four different models (one- and two-tissue compartment kinetic models, likelihood estimation in graphical analysis (LEGA; a bias-free alternative to the graphical method), and basis pursuit) along with fast noniterative approximations to the kinetic models. We considered four different outcome measures (total volume of distribution (V(T)), binding potential with (BP) and without (BP(1)), free-fraction adjustment, and specific-to-nonspecific equilibrium partition coefficient (BP(2))). To assess the performance of each model, we compared results using six different metrics (percent difference (PD) and within-subject mean sum of squares for reproducibility, interclass coefficient for reliability, variance across subjects, identifiability based on bootstrap resampling of residuals for each method, and time stability analysis to determine minimal required scanning time). We considered analysis of both at the voxel level and at the region of interest (ROI) level and compared results from these two approaches to assess agreement. We determined that 100 mins of scanning time is adequate and that for ROI-level analysis, LEGA gives best results. Average PD is 5.51 for V(T), 20.7 for BP, 17.2 for BP(1), and 16.5 for BP(2) across all regions. For voxel-level analysis we determined that the one-tissue compartment noniterative model is best.

Adolescent↗

PubMed1997

Rel/NF-kappa B transcription factors and I kappa B inhibitors: evolution from a unique common ancestor.

From the sequences of Rel/NF-kappa B and I kappa B proteins, we constructed an alignment of their Rel Homology Domain (RHD) and ankyrin repeat domain. Using this alignment, we performed tree reconstruction with both distance matrix and parsimony analysis and estimated the branching robustness using bootstrap resampling methods. We defined four subfamilies of Rel/NF-kappa B transcription factors: (i) cRel, RelA, RelB, Dorsal and Dif; (ii) NF-kappa B1 and NF-kappa B2; (iii) Relish and (iv) NF-AT factors, the most divergent members. Subfamilies I and II are clustered together whereas Relish diverged earlier than other Rel/NF-kappa B proteins. Three subfamilies of I kappa B inhibitors were also defined: (i) NF-kappa B1 and NF-kappa B2; (ii) close to subfamily I, the short I kappa B proteins I kappa B alpha, I kappa B beta and Bcl-3; (iii) Relish that diverged earlier than other I kappa B inhibitors. Our definition of groups and subfamilies fits to structural and functional features of the Rel/NF-kappa B and I kappa B proteins. We also showed that ankyrin repeats of NF-kappa B1, NF-kappa B2 and Relish are short I kappa B-specific ankyrin motifs. These proteins defining a link between Rel/NF-kappa B and I kappa B families, we propose that all these factors evolved from a common ancestral RHD-ankyrin structure within a unique superfamily, explaining the specificities of interaction between the different Rel/NF-kappa B dimers and the various I kappa B inhibitors.

Amino Acid Sequence↗

PubMed2000

Relationships between the endangered Pustertaler-Sprinzen and three related European cattle breeds as analysed with 20 microsatellite loci.

We estimated the genetic relationships between the endangered German Pustertaler-Sprinzen cattle breed and the Pinzgauer, Vosges and Simmental breeds--decided upon after consultation of the available historical literature. Within-breed diversity of the four breeds was also assessed. Twenty microsatellite markers were amplified in 27-50 unrelated individuals from populations of each breed. Within-breed variation was estimated from average heterozygosity values and mean number of alleles. Breed relationships were evaluated by genetic distance and a neighbour-joining tree was calculated from these estimates. Bootstrap resampling of loci tested the robustness of the tree topology obtained. A tree was also constructed from distance matrices using individual animals as operational taxonomic units. From both the average heterozygosity values and mean number of alleles calculated, the Pustertaler breed appears to be no more genetically impoverished than the other breeds analysed. The breed tree showed an 85% support for the Pustertaler-Pinzgauer grouping, and this result is echoed in the genetic distance values and allele-sharing individual tree.

Animals↗

PubMed2003

Simple estimation of the glomerular filtration rate in sick Thai children.

The objective of this study was to establish an appropriate formula for the estimation of creatinine clearance (CCr) in sick Thai children, and to evaluate the accuracy of using the Schwartz formula. Children aged between 0 and 19 years with various diseases and varying levels of renal function (but remained stable) were studied. Height in centimetres (L) and weight in kilograms (W), time of urine collection and urine volume were measured to provide urine flow (mL/min (V)) measurements. Body surface area (m2; SA) was also assessed. Quantitative urinary and plasma creatinine concentration (UCr and PCr, respectively) were determined. Creatinine clearance was calculated by using the following formula: UCr x V x 1.73/(PCr x SA). The linear association between CCr and L/PCr derived from these data was compared with the Schwartz formula by using bootstrap statistics. One-hundred and sixty children were studied. A least squares straight-line regression through the origin of CCr against L/PCr provided a good fit to the data. Our dataset revealed no evidence of an age or sex affect on the relationship. Creatinine clearance was estimated by using the following formula: 0.465 x (L/PCr), in which the calculated 95% confidence interval of the coefficient was 0.44-0.49. A comparison of this coefficient with that for the Schwartz formula for children aged > or =1 year (0.55), using 1000 bootstrapped resamples, showed an incompatibility between the two coefficients (P < 0.00005). In conclusion, we suggest estimating CCr in sick Thai children of either sex by using a modification of the Schwartz formula in which the coefficient equals 0.465.

Adolescent↗

PubMed2002

Automatic discrimination between supraventricular and ventricular tachycardia using a multilayer perceptron in implantable cardioverter defibrillators.

The morphological analysis of implantable cardioverter defibrillator (ICD) stored electrograms (EGM) using a multilayer perceptron (MLP) has been proposed for discrimination between supraventricular and ventricular arrhythmias. However, a reliable estimation of the accuracy of MLP methods is lacking. The aim of the study was to compare the morphology and spectrum-based MLP with more conventional morphology-based algorithms in a large series of ICD-stored episodes of arrhythmia. One set of ICD-stored electrograms was used for control and training purposes and a second one, consisting of spontaneous episodes in patients with dual chamber ICDs, for validation of the MLP performance. The correlation waveform analysis (CWA) and the EGM width criterion were compared with MLP methods. Bootstrap resampling techniques were used to extract the relevant information in the MLP training. The morphology-based MLP achieved better discrimination than any other method, with areas under the receiver operating characteristic (ROC) curve (tolerance intervals): 0.96 (0.81, 0.96) for MLP, 0.91 (0.77, 0.94) for CWA, and 0.68 (0.49, 0.78) for EGM width in the validation set. A specificity of 73.0% was obtained at 95% sensitivity, compared with 38.1% and 55.1% using CWA and EGM width criteria, respectively. In contrast, the generalization capabilities of spectral-based MLP methods are poor, showing a lower area under the ROC curve in the validation set. Time-domain MLP techniques may be useful for the morphological analysis of the intracardiac EGM signal stored by ICD devices. When properly trained and validated, these methods perform better than other commonly used morphological criteria for discrimination between supraventricular and ventricular arrhythmias.

Algorithms↗

PubMed2006

Template-driven gene selection procedure.

The hierarchical clustering and statistical techniques usually used to analyse microarray data do not inherently represent the underlying biology. Herein, a hybrid approach involving characteristics of both supervised and unsupervised learning is presented. This approach is based on template matching in which the interaction of the variables of inherent malignancy and the ability to express the malignant phenotype are modelled. Immortalised normal urothelial cells and bladder cancer cells of different malignancy were grown in conventional two-dimensional tissue culture and in three dimensions on extracellular matrices (ECMs) that were either permissive or restrictive for expression of the malignant phenotype. The transcriptome represents the effects of two variables--inherent malignancy and the modulatory effect of ECM. By assigning values to each of the biological variables of inherent malignancy and the ability to express the malignant phenotype, a template was constructed, which encapsulated the interaction between them. Gene expression correlating both positively and negatively with the template was observed, but when iterative correlations were carried out, the different models for the template converged on the same actual template. A subset of 21 genes was identified, which correlated with two a priori models or an optimised model above the 95% confidence limits identified in a bootstrap resampling with 5000 permutations of the data set. The correlation coefficients of expression of several genes were > 0.8. Analysis of upstream transcriptional regulatory elements (TREs) confirmed that these genes were not a randomly selected set of genes. Several TREs were identified as significantly over-expressed in the sample of 20 genes for which TREs were identified, and the high correlations of several genes were consistent with transcriptional co-regulation. The authors suggest that the template method can be used to identify a unique set of genes for further investigation.

Algorithms↗

PubMed1989

Evolutionary relationship of archaebacteria, eubacteria, and eukaryotes inferred from phylogenetic trees of duplicated genes.

All extant organisms are though to be classified into three primary kingdoms, eubacteria, eukaryotes, and archaebacteria. The molecular evolutionary studies on the origin and evolution of archaebacteria to date have been carried out by inferring a molecular phylogenetic tree of the primary kingdoms based on comparison of a single molecule from a variety of extant species. From such comparison, it was not possible to derive the exact evolutionary relationship among the primary kingdoms, because the root of the tree could not be determined uniquely. To overcome this difficulty, we compared a pair of duplicated genes, elongation factors Tu and G, and the alpha and beta subunits of ATPase, which are thought to have diverged by gene duplication before divergence of the primary kingdoms. Using each protein pair, we inferred a composite phylogenetic tree with two clusters corresponding to different proteins, from which the evolutionary relationship of the primary kingdoms is determined uniquely. The inferred composite trees reveal that archaebacteria are more closely related to eukaryotes than to eubacteria for all the cases. By bootstrap resamplings, this relationship is reproduced with probabilities of 0.96, 0.79, 1.0, and 1.0 for elongation factors Tu and G and for ATPase subunits alpha and beta, respectively. There are also several lines of evidence for the close sequence similarity between archaebacteria and eukaryotes. Thus we propose that this tree topology represents the general evolutionary relationship among the three primary kingdoms.

Adenosine Triphosphatases↗

PubMed1994

A fast random cost algorithm for physical mapping.

Ordering clones from a genomic library into physical maps of whole chromosomes presents a central computational/statistical problem in genetics. Here we present a physical mapping algorithm for creating ordered genomic libraries or contig maps by using a random cost approach [Berg, A. (1993) Nature (London) 361, 708-710]. This random cost algorithm is 5-10 times faster than existing physical mapping algorithms and has optimization performance comparable to existing procedures. The speedup in the algorithm makes practical the widespread use of bootstrap resampling to assess the statistical reliability of links in the physical map as well as the use of more elaborate physical mapping criteria to improve map quality. The random cost algorithm is illustrated by its application in assembling a physical map of chromosome IV from the filamentous fungus Aspergillus nidulans.

Aspergillus nidulans↗

PubMed2006

Occupational exposure to carbon/coke fibers in plants that produce green or calcined petroleum coke and potential health effects: 1. Fiber characteristics.

Carbon/coke fibers are found in bulk samples of calcined petroleum coke. Carbon/coke and other fibers, including calcium silicate, cellulose, gypsum, and iron silicate, have been found in exposure monitoring of workers who make or handle green or calcined petroleum coke. Carbon/coke fibers are not classified or regulated as carcinogens by any agency, and the available literature (summarized in this article) has not reported significant adverse health effects associated with exposure to these fibers or dusts containing these fibers. However, available epidemiological and toxicological studies have limitations that prevent a definitive assessment of carbon/coke fiber toxicity. Therefore, it is prudent to monitor and control workplace concentrations. Analyses by transmission electron microscopy (TEM) indicate that the carbon/coke fibers are amorphous, irregularly shaped, and generally rather short (94% less than 20 microm long). Nearly all carbon/ coke fibers satisfying NIOSH 7400 B counting criteria are detectable by phase-contrast optical microscopy (PCOM), which permits the use of a highly efficient sequential sampling strategy for analysis. Data are presented on the distribution of carbon/coke structure and fiber lengths and diameters. Bootstrap resampling results are presented to determine confidence intervals for structure/fiber length and diameter. Data on time-weighted average concentrations are given in a companion article, but nearly all time-weighted average carbon/coke fiber concentrations were beneath 0.1 fibers per milliliter.

Calcium Compounds↗

PubMed2005

A self-administered questionnaire to measure cigarette withdrawal symptoms: the Cigarette Withdrawal Scale.

Because few tobacco withdrawal scales have been submitted to appropriate validity analyses, we sought to develop and assess the validity of a new, self-administered scale measuring cigarette withdrawal symptoms. We generated the instrument content by conducting a qualitative survey of 404 smokers and ex-smokers. Then we tested 61 items on the Internet in 3,050 smokers and ex-smokers. Subsamples provided comprehensive retest data after 17 days (n = 1218) and smoking status after 41 days (n = 673). The study resulted in a 21-item, six-dimension scale labeled the Cigarette Withdrawal Scale (CWS-21). The six subscales cover the main components of nicotine or tobacco withdrawal in the Diagnostic and Statistical Manual of Mental Disorders and International Statistical Classification of Diseases and Related Health Problems and in qualitative data: Depression-anxiety, craving, irritability-impatience, appetite-weight gain, insomnia, and difficulty concentrating. The six scores had a satisfactory test-retest reliability (r = .60-.71) and a high internal consistency (Cronbach's alpha = .83-.96). The factor structure of the scale was robust in a bootstrap resampling procedure. In ex-smokers, all scores except appetite-weight gain and insomnia predicted relapse at 41-day follow-up. In recent ex-smokers who had quit smoking less than 14 days before baseline, all scores except appetite-weight gain decreased between baseline and the 17-day retest. In baseline ex-smokers who relapsed to smoking at the 17-day retest, appetite-weight gain decreased and craving increased between baseline and retest. CWS-21 is a reliable, valid, multidimensional measure of cigarette withdrawal symptoms that is sensitive to change over time and predicts relapse to smoking.

Adult↗

PubMed1999

Efficient identification of postdischarge surgical site infections: use of automated pharmacy dispensing information, administrative data, and medical record information.

Although most surgical site infections (SSIs) occur after hospital discharge, there is no efficient way to identify them. The utility of automated claims and electronic medical record data for this purpose was assessed in a cohort of 4086 nonobstetric procedures following which 96 postdischarge SSIs occurred. Coded diagnoses, tests, and treatments were assessed by use of recursive partitioning, with 10-fold cross-validation, and logistic regression with bootstrap resampling. Specific codes and combinations of codes identified a subset of 2% of all procedures among which 74% of SSIs had occurred. Accepting a specificity of 92% improved the sensitivity from 74% to 92%. Use of only hospital discharge diagnosis codes plus pharmacy dispensing data had sensitivity of 77% and specificity of 94%. All of these performance characteristics were better than questionnaire responses from patients or surgeons. Thus, information routinely collected by health care systems can be the basis of an efficient, largely passive, surveillance system for postdischarge SSIs.

Algorithms↗

PubMed2000

Diagnostic reference levels in interventional radiology.

Following the release of European Directive EU 97/43, radiodiagnostic facilities within the European Union are required to implement a system of patient dose reviews based on comparisons with European, national and local diagnostic reference levels (DRLs). Establishing these levels for typical interventional radiology examinations presents a problem as definition of 'typical' examinations can be difficult, patient numbers are limited and these procedures are often performed at a few specialist centres. This paper uses dose-area product (DAP) gathered over a period of 3 years from 40 fluoroscopy rooms to investigate potential difficulties when it comes to forming diagnostic reference levels for interventional radiology. Comparison of DAP distributions with standard complex (fluoroscopy based) examinations such as barium enema reveals considerably more variation for interventional procedures. Two methods of forming a DRL are compared: pooled patient DAP distributions versus a distribution of DAP per room. The bootstrap resampling method is then applied to DAP distributions to form a confidence interval for the chosen DRL statistic. Potential error on a DRL formed at a local level from a limited number of patient dose readings and x-ray rooms is significant. The results are reviewed in the wider context of DRLs in general radiology. For complex examinations, it is suggested that the function of the DRL is best served by setting DRLs based on pooled size-corrected patient DAP distributions rather than distributions of average DAP per room.

Dose-Response Relationship, Radiation↗

PubMed2000

Molecular epidemiology of HIV type 1 in a rural community in southwest Uganda.

The molecular epidemiology of a population-based cohort in a cluster of 15 villages in southwestern Uganda was investigated by sequencing part of the p24 gag gene and performing heteroduplex mobility assays (HMAs) of the V3 region of the env gene. Sequence and HMA data, obtained for 69 and 88 proviruses, respectively, showed that the clade A and D viruses were present at a ratio of about 0.67:1. No other clades were detected. Thirteen (22%) of 59 proviruses for which both gag and env data were obtained appeared to be recombinants. Although both clade A and D viruses were present in 13 of the villages, their distribution was unequal: for example, from env data 59% of clade A viruses were found in the eastern villages, compared with only 27% of clade D viruses. Phylogenetic (maximum likelihood) analysis of the p24 gag sequences showed a total of five clusters supported by bootstrap resampling values above or close to 75%. Four clusters were sexual partners, but there was no known sexual contact between the persons in the other cluster. The DNA sequences showed between 0.5 and 8.3% divergence from the cohort clade A or D consensus sequences. The sequences were not closely related to those published for other clade A or D proviruses.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Contig selection in physical mapping.

In physical mapping, one orders a set of genetic landmarks or a library of cloned fragments of DNA according to their position in the genome. Our approach to physical mapping divides the problem into smaller and easier subproblems by partitioning the probe set into independent parts (probe contigs). For this purpose we introduce a new distance function between probes, the averaged rank distance (ARD) derived from bootstrap resampling of the raw data. The ARD measures the pairwise distances of probes within a contig and smoothes the distances of probes across different contigs. It shows distinct jumps at contig borders. This makes it appropriate for contig selection by clustering. We have designed a physical mapping algorithm that makes use of these observations and seems to be particularly well suited to the delineation of reliable contigs. We evaluated our method on data sets from two physical mapping projects. On data from the recently sequenced bacterium Xylella fastidiosa, the probe contig set produced by the new method was evaluated using the probe order derived from the sequence information. Our approach yielded a basically correct contig set. On this data we also compared our method to an approach which uses the number of supporting clones to determine contigs. Our map is much more accurate. In comparison to a physical map of Pasteurella haemolytica that was computed using simulated annealing, the newly computed map is considerably cleaner. The results of our method have already proven helpful for the design of experiments aimed at further improving the quality of a map.

Algorithms↗

PubMed2005

Estimating misclassification error with small samples via bootstrap cross-validation.

MOTIVATION: Estimation of misclassification error has received increasing attention in clinical diagnosis and bioinformatics studies, especially in small sample studies with microarray data. Current error estimation methods are not satisfactory because they either have large variability (such as leave-one-out cross-validation) or large bias (such as resubstitution and leave-one-out bootstrap). While small sample size remains one of the key features of costly clinical investigations or of microarray studies that have limited resources in funding, time and tissue materials, accurate and easy-to-implement error estimation methods for small samples are desirable and will be beneficial. RESULTS: A bootstrap cross-validation method is studied. It achieves accurate error estimation through a simple procedure with bootstrap resampling and only costs computer CPU time. Simulation studies and applications to microarray data demonstrate that it performs consistently better than its competitors. This method possesses several attractive properties: (1) it is implemented through a simple procedure; (2) it performs well for small samples with sample size, as small as 16; (3) it is not restricted to any particular classification rules and thus applies to many parametric or non-parametric methods.

Algorithms↗

PubMed1995

A second superoxide dismutase gene in the medfly, Ceratitis capitata.

We report the first case of two Cu/Zn Sod genes (ccSod1 and ccSod2) that have been cloned and sequenced from an insect, the medfly, Ceratitis capitata. Biochemical evidence suggested the presence of two Sod genes in the medfly. The two genes are isolated using different molecular strategies: ccSod1 via cross-hybridization to a genomic library using a heterologous probe and ccSod2 from cDNA using a homologous probe generated by PCR. Sequence analysis shows that ccSod1 and ccSod2 are different genes. The inferred amino sequences show that all essential residues of the active site are strictly conserved, which suggests both genes encode functional Cu/Zn superoxide dismutase (SOD). Phylogenetic analysis by the maximum parsimony method with bootstrap resampling of previously known Cu/Zn SOD reveals two monophyletic groups, vertebrates and insects. The position of ccSOD2 in this phylogeny is undefined with respect to dipteran ccSOD1, vertebrate, plant, fungal, and extracellular Cu/Zn SOD, which suggests that the duplication detected in Ceratitis is ancient, perhaps as old as the origins of the arthropod phylum in the Cambrian more than 500 million years ago. In situ hybridization to polytene chromosomes places the genes on different chromosomes, which is consistent with an ancient gene duplication.

Amino Acid Sequence↗