Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics.

Integrating single nucleotide polymorphism (SNP) p-values from genome-wide association studies (GWAS) across genes and pathways is a strategy to improve statistical power and gain biological insight. Here, we present Pascal (Pathway scoring algorithm), a powerful tool for computing gene and pathway scores from SNP-phenotype association summary statistics. For gene score computation, we implemented analytic and efficient numerical solutions to calculate test statistics. We examined in particular the sum and the maximum of chi-squared statistics, which measure the strongest and the average association signals per gene, respectively. For pathway scoring, we use a modified Fisher method, which offers not only significant power improvement over more traditional enrichment strategies, but also eliminates the problem of arbitrary threshold selection inherent in any binary membership based pathway enrichment approach. We demonstrate the marked increase in power by analyzing summary statistics from dozens of large meta-studies for various traits. Our extensive testing indicates that our method not only excels in rigorous type I error control, but also results in more biologically meaningful discoveries.

Nota sobre a biologia de "Microdon tigrinus" (Diptera: Syrphidae), parasito social de "Acromyrmex coronatus" (Hymenoptera: Formicidae)

The fly of the syrphid Microdon tigrinus is a specific social parasite of leaf-cutting ant, Acromyrmex coronatus. Six colonies of Acromyrmex coronatus were collected in plastic containers, which there was a layer of 1 cm of plaster, with the purpose of maintaining the humidity of fungus culture. Larvae of social parasite were separate for the establishment of instars number, through morphometric study. The data were measured of 165 larvae, using spiracle (length (Ls), width (Ws) and distance between spiracle (Ds)). After that, the morphometric data obtained for the larvae were submitted to cluster analysis by Wong's hybrid method, which produces the adequate number of groups through pseudo F-statistics and pseudo t-squared statistics. The three morphometric variables studied permitted grouping of larvae into the following three distinct groups: cluster 1 [long dash] consisting of 55 larvae (Ls=0.177[plus or minus]0.026, Ws=0.163[plus or minus]0.030, Ds=0.052[plus or minus]0.008 mm); cluster 2 - consisting of 20 larvae (Ls=0.631[plus or minus]0.065, Ws=0.630[plus or minus]0.049, Ds=0.065[plus or minus]0.018 mm); cluster 3 - consisting of 90 larvae (Ls=1.294[plus or minus]0.062, Ws=1.308[plus or minus]0.069, Ds=0.140[plus or minus]0.018 mm). of the all couples, only 1 obtained success in the mating, and the female, after 24 hours, began the oviposition. The female layed 76 eggs in a period of 6 days, after that, her death. The larvae emerged in the seventh day (incubation period [plus or minus] 7 days). From 76 eggs, 54 were viable, with a viability of 71.05%. This study contributes to the knowledge of Microdon tigrinus biology of, a social parasite poorly studied in Brazil.

Analysis of procedures used in tooth avulsion by 100 dental surgeons

Accurate diagnosis and adequate treatment plan may constitute very complex tasks, particularly in tooth avulsion, because several variables are involved. In addition to the technical knowledge and clinical experience directed toward the quality of treatment, patient education may favorably influence the survival of replanted teeth. The aim of this study was to analyze the procedures used in the management of tooth avulsion by 100 dental surgeons (DSs). Thus, by means of a descriptive questionnaire, information was obtained about the profile of the professionals interviewed, procedures used in cases of tooth avulsion, and patient orientation and education. One hundred properly filled questionnaires were obtained. Descriptive statistics was used for the data, and the chi-squared statistics was employed (EPI-INFO 3.2 software). According to the results, this type of trauma is part of the routine of 15 DSs, although 71 have reported some experience with avulsed,teeth. Great deficiencies were found regarding root surface treatment and occlusal adjustment. Positive findings were related to socket treatment, adjunctive therapy, and patient education and orientation (extra-alveolar period, storage medium, manipulation of the avulsed tooth, replantation by the own patient). It was possible to conclude that 47.5% of the procedures reported by, 100 professionals interviewed are adequate, and patient education is favorable in 87.7% of cases, a fact that can positively interfere with the prognosis of tooth replantation.

A Stochastic Approach for Finding of Semantically Related Words

2000 Mathematics Subject Classification: 62P99, 68T50

Aitchison Geometry for Probability and Likelihood as a new approach to mathematical statistics

The Aitchison vector space structure for the simplex is generalized to a Hilbert space structure A2(P) for distributions and likelihoods on arbitrary spaces. Centralnotations of statistics, such as Information or Likelihood, can be identified in the algebraical structure of A2(P) and their corresponding notions in compositional data analysis, such as Aitchison distance or centered log ratio transform.In this way very elaborated aspects of mathematical statistics can be understoodeasily in the light of a simple vector space structure and of compositional data analysis. E.g. combination of statistical information such as Bayesian updating,combination of likelihood and robust M-estimation functions are simple additions/perturbations in A2(Pprior). Weighting observations corresponds to a weightedaddition of the corresponding evidence.Likelihood based statistics for general exponential families turns out to have aparticularly easy interpretation in terms of A2(P). Regular exponential families formfinite dimensional linear subspaces of A2(P) and they correspond to finite dimensionalsubspaces formed by their posterior in the dual information space A2(Pprior).The Aitchison norm can identified with mean Fisher information. The closing constant itself is identified with a generalization of the cummulant function and shown to be Kullback Leiblers directed information. Fisher information is the local geometry of the manifold induced by the A2(P) derivative of the Kullback Leibler information and the space A2(P) can therefore be seen as the tangential geometry of statistical inference at the distribution P.The discussion of A2(P) valued random variables, such as estimation functionsor likelihoods, give a further interpretation of Fisher information as the expected squared norm of evidence and a scale free understanding of unbiased reasoning

Improving small area estimation by combining surveys: new perspectives in regional statistics

A national survey designed for estimating a specific population quantity is sometimes used for estimation of this quantity also for a small area, such as a province. Budget constraints do not allow a greater sample size for the small area, and so other means of improving estimation have to be devised. We investigate such methods and assess them by a Monte Carlo study. We explore how a complementary survey can be exploited in small area estimation. We use the context of the Spanish Labour Force Survey (EPA) and the Barometer in Spain for our study.

Aitchison Geometry for Probability and Likelihood as a new approach to mathematical statistics

The Aitchison vector space structure for the simplex is generalized to a Hilbert space structure A2(P) for distributions and likelihoods on arbitrary spaces. Central notations of statistics, such as Information or Likelihood, can be identified in the algebraical structure of A2(P) and their corresponding notions in compositional data analysis, such as Aitchison distance or centered log ratio transform. In this way very elaborated aspects of mathematical statistics can be understood easily in the light of a simple vector space structure and of compositional data analysis. E.g. combination of statistical information such as Bayesian updating, combination of likelihood and robust M-estimation functions are simple additions/ perturbations in A2(Pprior). Weighting observations corresponds to a weighted addition of the corresponding evidence. Likelihood based statistics for general exponential families turns out to have a particularly easy interpretation in terms of A2(P). Regular exponential families form finite dimensional linear subspaces of A2(P) and they correspond to finite dimensional subspaces formed by their posterior in the dual information space A2(Pprior). The Aitchison norm can identified with mean Fisher information. The closing constant itself is identified with a generalization of the cummulant function and shown to be Kullback Leiblers directed information. Fisher information is the local geometry of the manifold induced by the A2(P) derivative of the Kullback Leibler information and the space A2(P) can therefore be seen as the tangential geometry of statistical inference at the distribution P. The discussion of A2(P) valued random variables, such as estimation functions or likelihoods, give a further interpretation of Fisher information as the expected squared norm of evidence and a scale free understanding of unbiased reasoning

Three Bartlett-type corrections for score statistics in symmetric nonlinear regression models

We present simple matrix formulae for corrected score statistics in symmetric nonlinear regression models. The corrected score statistics follow more closely a chi (2) distribution than the classical score statistic. Our simulation results indicate that the corrected score tests display smaller size distortions than the original score test. We also compare the sizes and the powers of the corrected score tests with bootstrap-based score tests.

MODIFIED TEST STATISTICS BY INTER-VOXEL VARIANCE SHRINKAGE WITH AN APPLICATION TO fMRI

Functional Magnetic Resonance Imaging (fMRI) is a non-invasive technique which is commonly used to quantify changes in blood oxygenation and flow coupled to neuronal activation. One of the primary goals of fMRI studies is to identify localized brain regions where neuronal activation levels vary between groups. Single voxel t-tests have been commonly used to determine whether activation related to the protocol differs across groups. Due to the generally limited number of subjects within each study, accurate estimation of variance at each voxel is difficult. Thus, combining information across voxels in the statistical analysis of fMRI data is desirable in order to improve efficiency. Here we construct a hierarchical model and apply an Empirical Bayes framework on the analysis of group fMRI data, employing techniques used in high throughput genomic studies. The key idea is to shrink residual variances by combining information across voxels, and subsequently to construct an improved test statistic in lieu of the classical t-statistic. This hierarchical model results in a shrinkage of voxel-wise residual sample variances towards a common value. The shrunken estimator for voxelspecific variance components on the group analyses outperforms the classical residual error estimator in terms of mean squared error. Moreover, the shrunken test-statistic decreases false positive rate when testing differences in brain contrast maps across a wide range of simulation studies. This methodology was also applied to experimental data regarding a cognitive activation task.

What Is Expected From A Facial Trauma Caused By Violence?

The aim of this retrospective study was to compare the peculiarities of maxillofacial injuries caused by interpersonal violence with other etiologic factors. Medical records of 3,724 patients with maxillofacial injuries in São Paulo state (Brazil) were retrospectively analyzed. The data were submitted to statistical analysis (simple descriptive statistics and Chi-squared test) using SPSS 18.0 software. Data of 612 patients with facial injuries caused by violence were analyzed. The majority of the patients were male (81%; n = 496), with a mean age of 31.28 years (standard deviation of 13.33 years). These patients were more affected by mandibular and nose fractures, when compared with all other patients (P < 0.01), although fewer injuries were recorded in other body parts (χ(2) = 17.54; P < 0.01); Victims of interpersonal violence exhibited more injuries when the neurocranium was analyzed in isolation (χ(2) = 6.85; P < 0.01). Facial trauma due to interpersonal violence seem to be related to a higher rate of facial fractures and lacerations when compared to all patients with facial injuries. Prominent areas of the face and neurocranium were more affected by injuries.

An empirical evaluation of imputation accuracy for association statistics reveals increased type-I error rates in genome-wide associations

Background: Genome wide association studies (GWAS) are becoming the approach of choice to identify genetic determinants of complex phenotypes and common diseases. The astonishing amount of generated data and the use of distinct genotyping platforms with variable genomic coverage are still analytical challenges. Imputation algorithms combine directly genotyped markers information with haplotypic structure for the population of interest for the inference of a badly genotyped or missing marker and are considered a near zero cost approach to allow the comparison and combination of data generated in different studies. Several reports stated that imputed markers have an overall acceptable accuracy but no published report has performed a pair wise comparison of imputed and empiric association statistics of a complete set of GWAS markers. Results: In this report we identified a total of 73 imputed markers that yielded a nominally statistically significant association at P < 10(-5) for type 2 Diabetes Mellitus and compared them with results obtained based on empirical allelic frequencies. Interestingly, despite their overall high correlation, association statistics based on imputed frequencies were discordant in 35 of the 73 (47%) associated markers, considerably inflating the type I error rate of imputed markers. We comprehensively tested several quality thresholds, the haplotypic structure underlying imputed markers and the use of flanking markers as predictors of inaccurate association statistics derived from imputed markers. Conclusions: Our results suggest that association statistics from imputed markers showing specific MAF (Minor Allele Frequencies) range, located in weak linkage disequilibrium blocks or strongly deviating from local patterns of association are prone to have inflated false positive association signals. The present study highlights the potential of imputation procedures and proposes simple procedures for selecting the best imputed markers for follow-up genotyping studies.

Recovery of the star formation history of the LMC from the VISTA survey of the Magellanic system

The VISTA near infrared survey of the Magellanic System (VMC) will provide deep YJK(s) photometry reaching stars in the oldest turn-off point throughout the Magellanic Clouds (MCs). As part of the preparation for the survey, we aim to access the accuracy in the star formation history (SFH) that can be expected from VMC data, in particular for the Large Magellanic Cloud (LMC). To this aim, we first simulate VMC images containing not only the LMC stellar populations but also the foreground Milky Way (MW) stars and background galaxies. The simulations cover the whole range of density of LMC field stars. We then perform aperture photometry over these simulated images, access the expected levels of photometric errors and incompleteness, and apply the classical technique of SFH-recovery based on the reconstruction of colour-magnitude diagrams (CMD) via the minimisation of a chi-squared-like statistics. We verify that the foreground MW stars are accurately recovered by the minimisation algorithms, whereas the background galaxies can be largely eliminated from the CMD analysis due to their particular colours and morphologies. We then evaluate the expected errors in the recovered star formation rate as a function of stellar age, SFR(t), starting from models with a known age-metallicity relation (AMR). It turns out that, for a given sky area, the random errors for ages older than similar to 0.4 Gyr seem to be independent of the crowding. This can be explained by a counterbalancing effect between the loss of stars from a decrease in the completeness and the gain of stars from an increase in the stellar density. For a spatial resolution of similar to 0.1 deg(2), the random errors in SFR(t) will be below 20% for this wide range of ages. On the other hand, due to the lower stellar statistics for stars younger than similar to 0.4 Gyr, the outer LMC regions will require larger areas to achieve the same level of accuracy in the SFR( t). If we consider the AMR as unknown, the SFH-recovery algorithm is able to accurately recover the input AMR, at the price of an increase of random errors in the SFR(t) by a factor of about 2.5. Experiments of SFH-recovery performed for varying distance modulus and reddening indicate that these parameters can be determined with (relative) accuracies of Delta(m-M)(0) similar to 0.02 mag and Delta E(B-V) similar to 0.01 mag, for each individual field over the LMC. The propagation of these errors in the SFR(t) implies systematic errors below 30%. This level of accuracy in the SFR(t) can reveal significant imprints in the dynamical evolution of this unique and nearby stellar system, as well as possible signatures of the past interaction between the MCs and the MW.

Statistics of opinion domains of the majority-vote model on a square lattice

The existence of juxtaposed regions of distinct cultures in spite of the fact that people's beliefs have a tendency to become more similar to each other's as the individuals interact repeatedly is a puzzling phenomenon in the social sciences. Here we study an extreme version of the frequency-dependent bias model of social influence in which an individual adopts the opinion shared by the majority of the members of its extended neighborhood, which includes the individual itself. This is a variant of the majority-vote model in which the individual retains its opinion in case there is a tie among the neighbors' opinions. We assume that the individuals are fixed in the sites of a square lattice of linear size L and that they interact with their nearest neighbors only. Within a mean-field framework, we derive the equations of motion for the density of individuals adopting a particular opinion in the single-site and pair approximations. Although the single-site approximation predicts a single opinion domain that takes over the entire lattice, the pair approximation yields a qualitatively correct picture with the coexistence of different opinion domains and a strong dependence on the initial conditions. Extensive Monte Carlo simulations indicate the existence of a rich distribution of opinion domains or clusters, the number of which grows with L(2) whereas the size of the largest cluster grows with ln L(2). The analysis of the sizes of the opinion domains shows that they obey a power-law distribution for not too large sizes but that they are exponentially distributed in the limit of very large clusters. In addition, similarly to other well-known social influence model-Axelrod's model-we found that these opinion domains are unstable to the effect of a thermal-like noise.

Protein fold recognition without Boltzmann statistics or explicit physical basis

We present a fast method for finding optimal parameters for a low-resolution (threading) force field intended to distinguish correct from incorrect folds for a given protein sequence. In contrast to other methods, the parameterization uses information from >10(7) misfolded structures as well as a set of native sequence-structure pairs. In addition to testing the resulting force field's performance on the protein sequence threading problem, results are shown that characterize the number of parameters necessary for effective structure recognition.