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In many epidemiology studies, family data with survival endpoints are collected to investigate the association between risk factors and disease incidence. Sometimes the risk of the disease may change when a certain risk factor exceeds a certain threshold. Finding this threshold value could be important for disease risk prediction and diseases prevention. In this work, we propose a change-point proportional hazards model for clustered event data. The model incorporates the unknown threshold of a continuous variable as a change point in the regression. The marginal pseudo-partial likelihood functions are maximized for estimating the regression coefficients and the unknown change point. We develop a supremum test based on robust score statistics to test the existence of the change point. The inference for the change point is based on the m out of n bootstrap. We establish the consistency and asymptotic distributions of the proposed estimators. The finite-sample performance of the proposed method is demonstrated via extensive simulation studies. Finally, the Strong Heart Family Study dataset is analyzed to illustrate the methods. [ABSTRACT FROM AUTHOR]

The Galaxy And Mass Assembly (GAMA) survey has obtained spectra of over 230 000 targets using the Anglo-Australian Telescope. To homogenize the redshift measurements and improve the reliability, a fully automatic redshift code was developed (autoz). The measurements were made using a cross-correlation method for both the absorption- and the emission-line spectra. Large deviations in the high-pass-filtered spectra are partially clipped in order to be robust against uncorrected artefacts and to reduce the weight given to single-line matches. A single figure of merit (FOM) was developed that puts all template matches on to a similar confidence scale. The redshift confidence as a function of the FOM was fitted with a tanh function using a maximum likelihood method applied to repeat observations of targets. The method could be adapted to provide robust automatic redshifts for other large galaxy redshift surveys. For the GAMA survey, there was a substantial improvement in the reliability of assigned redshifts and in the lowering of redshift uncertainties with a median velocity uncertainty of 33 km s−1. [ABSTRACT FROM AUTHOR]

Motivation: Gene set analysis is a popular method for large-scale genomic studies. Because genes that have common biological features are analyzed jointly, gene set analysis often achieves better power and generates more biologically informative results. With the advancement of technologies, genomic studies with multi-platform data have become increasingly common. Several strategies have been proposed that integrate genomic data from multiple platforms to perform gene set analysis. To evaluate the performances of existing integrative gene set methods under various scenarios, we conduct a comparative simulation analysis based on The Cancer Genome Atlas breast cancer dataset.Results: We find that existing methods for gene set analysis are less effective when sample heterogeneity exists. To address this issue, we develop three methods for multi-platform genomic data with heterogeneity: two non-parametric methods, multi-platform Mann–Whitney statistics and multi-platform outlier robust T-statistics, and a parametric method, multi-platform likelihood ratio statistics. Using simulations, we show that the proposed multi-platform Mann–Whitney statistics method has higher power for heterogeneous samples and comparable performance for homogeneous samples when compared with the existing methods. Our real data applications to two datasets of The Cancer Genome Atlas also suggest that the proposed methods are able to identify novel pathways that are missed by other strategies.Availability and implementation: http://www4.stat.ncsu.edu/∼jytzeng/Software/Multiplatform_gene_set_analysis/Contact: john.hu@omicsoft.com, jhu7@ncsu.eduSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM PUBLISHER]

The robust statistical model of a Gaussian core contaminated by outlying data that underlies robust estimation of the magnetotelluric (MT) response function has been re-examined. The residuals from robust estimators are systematically long tailed compared to a distribution based on the Gaussian, and hence are inconsistent with the robust model. Instead, MT data are pervasively described by the alpha stable distribution family whose variance and sometimes mean are undefined. A maximum likelihood estimator (MLE) that exploits the stable nature of MT data is formulated, and its two-stage implementation in which stable parameters are first fit to the data and then the MT responses are solved for is described. The MLE is shown to be inherently robust, but differs from the conventional robust estimator because it is based on a model derived from the data, while robust estimators are ad hoc, being based on the robust model that is inconsistent with actual data. Propriety versus impropriety of the complex MT response was investigated, and a likelihood ratio test for propriety and its null distribution was established. The Cramér-Rao lower bounds for the covariance matrix of proper and improper MT responses were specified.The MLE was applied to exemplar long period and broad-band data sets from South Africa. Both are shown to be significantly stably distributed using the Kolmogorov–Smirnov goodness of fit and Ansari-Bradley non-parametric dispersion tests. Impropriety of the MT responses at both sites is pervasive, hence the improper Cramér-Rao bound was used to estimate the MLE covariance. The MLE is shown to be nearly unbiased and well described by a Gaussian distribution based on bootstrap simulation. The MLE was compared to a conventional robust estimator, establishing that the standard errors of the former are systematically smaller than for the latter and that the standardized differences between them exhibit excursions that are both too frequent and too large to be described by a Gaussian model. This is ascribed to pervasive bias of the robust estimator that is to some degree obscured by their systematically large confidence bounds. Finally, a series of topics for further investigation is proposed. [ABSTRACT FROM PUBLISHER]

Empirical Bayes methods have been extensively used for microarray data analysis by modeling the large number of unknown parameters as random effects. Empirical Bayes allows borrowing information across genes and can automatically adjust for multiple testing and selection bias. However, the standard empirical Bayes model can perform poorly if the assumed working prior deviates from the true prior. This paper proposes a new rank-conditioned inference in which the shrinkage and confidence intervals are based on the distribution of the error conditioned on rank of the data. Our approach is in contrast to a Bayesian posterior, which conditions on the data themselves. The new method is almost as efficient as standard Bayesian methods when the working prior is close to the true prior, and it is much more robust when the working prior is not close. In addition, it allows a more accurate (but also more complex) non-parametric estimate of the prior to be easily incorporated, resulting in improved inference. The new method’s prior robustness is demonstrated via simulation experiments. Application to a breast cancer gene expression microarray dataset is presented. Our R package rank.Shrinkage provides a ready-to-use implementation of the proposed methodology. [ABSTRACT FROM PUBLISHER]

In this article, we develop a linear supervised subspace learning method called locality-based discriminant neighborhood embedding (LDNE), which can take advantage of the underlying submanifold-based structures of the data for classification. Our LDNE method can simultaneously consider both ‘locality’ of locality preserving projection (LPP) and ‘discrimination’ of discriminant neighborhood embedding (DNE) in manifold learning. It can find an embedding that not only preserves local information to explore the intrinsic submanifold structure of data from the same class, but also enhances the discrimination among submanifolds from different classes. To investigate the performance of LDNE, we compare it with the state-of-the-art dimensionality reduction techniques such as LPP and DNE on publicly available datasets. Experimental results show that our LDNE can be an effective and robust method for classification. [ABSTRACT FROM PUBLISHER]

Motivation: Inferring global regulatory networks (GRNs) from genome-wide data is a computational challenge central to the field of systems biology. Although the primary data currently used to infer GRNs consist of gene expression and proteomics measurements, there is a growing abundance of alternate data types that can reveal regulatory interactions, e.g. ChIP-Chip, literature-derived interactions, protein–protein interactions. GRN inference requires the development of integrative methods capable of using these alternate data as priors on the GRN structure. Each source of structure priors has its unique biases and inherent potential errors; thus, GRN methods using these data must be robust to noisy inputs.Results: We developed two methods for incorporating structure priors into GRN inference. Both methods [Modified Elastic Net (MEN) and Bayesian Best Subset Regression (BBSR)] extend the previously described Inferelator framework, enabling the use of prior information. We test our methods on one synthetic and two bacterial datasets, and show that both MEN and BBSR infer accurate GRNs even when the structure prior used has significant amounts of error (>90% erroneous interactions). We find that BBSR outperforms MEN at inferring GRNs from expression data and noisy structure priors.Availability and implementation: Code, datasets and networks presented in this article are available at http://bonneaulab.bio.nyu.edu/software.html.Contact: bonneau@nyu.eduSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM PUBLISHER]

A great deal of effort is currently being devoted to understanding, estimating and removing systematic errors in cosmological data. In the particular case of Type Ia supernovae, systematics are starting to dominate the error budget. Here we propose a Bayesian tool for carrying out a systematic search for systematic contamination. This serves as an extension to the standard goodness-of-fit tests and allows not only to cross-check raw or processed data for the presence of systematics but also to pin-point the data that are most likely contaminated. We successfully test our tool with mock catalogues and conclude that the Union2.1 data do not possess a significant amount of systematics. Finally, we show that if one includes in Union2.1 the supernovae that originally failed the quality cuts, our tool signals the presence of systematics at over 3.8σ confidence level. [ABSTRACT FROM AUTHOR]

Here we present first-order results detailing the Anatolian crustal from receiver function analysis of data from approximately 300 stations within Turkey. Seismic data from the Kandilli Observatory array (KOERI; KO), the National Seismic Network of Turkey (AFAD-DAD; TU) and available IRIS data from the Northern Anatolian Fault experiment (YL) for the period between 2005 and 2010 is analysed. We calculate receiver functions in the frequency domain using water-level deconvolution. The results are analysed using a combination of H–K stacking and depth stacking to determine robust Moho conversion depths and VP/Vs ratios across Anatolia. We detect a deep Moho in eastern Anatolia of up to ∼55 km, a generally normal Moho in Central Anatolia of ∼37–47 km and a thinned Moho in western Anatolia and Cyprus of ∼30 km. The VP/Vs ratio across the Anatolian Plate is generally slightly elevated; regions of extremely high VP/Vs ratio (>1.85) can be associated with recent volcanism in eastern and central Anatolia. High VP/Vs ratio measurements (>1.85) in western Anatolia may be indicative of partial melt in the lower crust associated with regional extension. [ABSTRACT FROM AUTHOR]

Background Population structure (PS), including population stratification and admixture, is a significant confounder in genome-wide association studies (GWAS), as it may produce spurious associations. Random forest (RF) has been increasingly applied in GWAS data analysis because of its advantage in analysing high dimensional genetic data. RF creates importance measures for single nucleotide polymorphisms (SNPs), which are helpful for feature selections. However, if PS is not appropriately corrected, RF tends to give high importance to disease-unrelated SNPs with different frequencies of allele or genotype among subpopulations, leading to inaccurate results.Methods In this study, the authors propose to correct for the confounding effect of PS by including the information of PS in RF analysis. The correction procedure starts by extracting the information of PS using EIGENSTRAT or multi-dimensional scaling clustering procedure from a large number of structure inference SNPs. Phenotype and genotypes adjusted by the information of PS are then used as the outcome and predictors in RF analysis.Results Extensive simulations indicate that the importance measure of the causal SNP is increased following the PS correction. By analysing a real dataset, the proposed correction removes the spurious association between the lactase gene and height.Conclusion The authors propose a simple method to correct for PS in RF analysis on GWAS data. Further studies in real GWAS datasets are required to validate the robustness of the proposed approach. [ABSTRACT FROM PUBLISHER]

We modified the phylogenetic program MrBayes 3.1.2 to incorporate the compound Dirichlet priors for branch lengths proposed recently by Raimala, Zhu, and Yang (2012. Tail paradox, partial identifiability and influential priors in Bayesian branch length inference. Mol. Biol. Evol. 29:325-335.) as a solution to the problem of branch-length overestimation in Bayesian phylogenetic inference. The compound Dirichlet prior specifies a fairly diffuse prior on the tree length (the sum of branch lengths) and uses a Dirichlet distribution to partition the tree length into branch lengths. Six problematic data sets originally analyzed by Brown, Hedtke, Lemmon, and Lemmon (2010. When trees grow too long: investigating the causes of highly inaccurate Bayesian branch-length estimates. Syst. Biol. 59:145-161) are reanalyzed using the modified version of MrBayes to investigate properties of Bayesian branch-length estimation using the new priors. While the default exponential priors for branch lengths produced extremely long trees, the compound Dirichlet priors produced posterior estimates that are much closer to the maximum likelihood estimates. Furthermore, the posterior tree lengths were quite robust to changes in the parameter values in the compound Dirichlet priors, for example, when the prior mean of tree length changed over several orders of magnitude. Our results suggest that the compound Dirichlet priors may be useful for correcting branchlength overestimation in phylogenetic analyses of empirical data sets. [ABSTRACT FROM AUTHOR]

Motivation: microRNAs are short non-coding RNAs that regulate gene expression by inhibiting target mRNA genes. Next-generation sequencing combined with bioinformatics analyses provide an opportunity to predict numerous novel miRNAs. The efficiency of these predictions relies on the set of positive and negative controls used. We demonstrate that commonly used positive and negative controls may be unreliable and provide a rational methodology with which to replace them.Contact: w.ritchie@centenary.org.auSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

There are copula-based statistical models in the literature for regression with dependent data such as clustered and longitudinal overdispersed counts, for which parameter estimation and inference are straightforward. For situations where the main interest is in the regression and other univariate parameters and not the dependence, we propose a “weighted scores method”, which is based on weighting score functions of the univariate margins. The weight matrices are obtained initially fitting a discretized multivariate normal distribution, which admits a wide range of dependence. The general methodology is applied to negative binomial regression models. Asymptotic and small-sample efficiency calculations show that our method is robust and nearly as efficient as maximum likelihood for fully specified copula models. An illustrative example is given to show the use of our weighted scores method to analyze utilization of health care based on family characteristics. [ABSTRACT FROM PUBLISHER]

Motivation: Binary datasets represent a compact and simple way to store data about the relationships between a group of objects and their possible properties. In the last few years, different biclustering algorithms have been specially developed to be applied to binary datasets. Several approaches based on matrix factorization, suffix trees or divide-and-conquer techniques have been proposed to extract useful biclusters from binary data, and these approaches provide information about the distribution of patterns and intrinsic correlations.Results: A novel approach to extracting biclusters from binary datasets, BiBit, is introduced here. The results obtained from different experiments with synthetic data reveal the excellent performance and the robustness of BiBit to density and size of input data. Also, BiBit is applied to a central nervous system embryonic tumor gene expression dataset to test the quality of the results. A novel gene expression preprocessing methodology, based on expression level layers, and the selective search performed by BiBit, based on a very fast bit-pattern processing technique, provide very satisfactory results in quality and computational cost. The power of biclustering in finding genes involved simultaneously in different cancer processes is also shown. Finally, a comparison with Bimax, one of the most cited binary biclustering algorithms, shows that BiBit is faster while providing essentially the same results.Availability: The source and binary codes, the datasets used in the experiments and the results can be found at: http://www.upo.es/eps/bigs/BiBit.htmlContact: dsrodbae@upo.esSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation: Recently, De Neve et al. proposed a modification of the Wilcoxon–Mann–Whitney (WMW) test for assessing differential expression based on RT-qPCR data. Their test, referred to as the unified WMW (uWMW) test, incorporates a robust and intuitive normalization and quantifies the probability that the expression from one treatment group exceeds the expression from another treatment group. However, no software package for this test was available yet.Results: We have developed a Bioconductor package for analyzing RT-qPCR data with the uWMW test. The package also provides graphical tools for visualizing the effect sizes.Availability and implementation: The unifiedWMWqPCR package and its user documentation can be obtained through Bioconductor.Contact: JanR.DeNeve@UGent.be [ABSTRACT FROM AUTHOR]

Summary: Graphical Gaussian models (GGMs) are a promising approach to identify gene regulatory networks. Such models can be robustly inferred by solving the sparse inverse covariance selection (SICS) problem. With the high dimensionality of genomics data, fast methods capable of solving large instances of SICS are needed.We developed a novel network modeling tool, Ultranet, that solves the SICS problem with significantly improved efficiency. Ultranet combines a range of mathematical and programmatical techniques, exploits the structure of the SICS problem and enables computation of genome-scale GGMs without compromising analytic accuracy.Availability and implementation: Ultranet is implemented in C++ and available at www.broadinstitute.org/ultranet.Contact: bnilsson@broadinstitute.org or bjorn.nilsson@med.lu.seSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]