Abstract:
:Polytomous phenotypes arise when a disease has multiple subtypes or when two dichotomous phenotypes are analyzed simultaneously. Few software programs offer the option to analyze such phenotypes in family studies, and none implements conditional polytomous logistic regression for within-family analysis robust to population stratification. We introduce Polyunphased, an extension to polytomous phenotypes of the Unphased package, a flexible software tool for genetic association analysis in nuclear families. Like Unphased, Polyunphased is written in C++ and runs from the command line or from a Java graphical user interface. Most Unphased options remain available in Polyunphased, including those handling missing parental genotypes while preserving robustness to population stratification, and the modelling options. Simulation studies confirmed the expected statistical behaviour of the maximum likelihood estimates of the association parameters of the conditional logistic regression model when the corresponding association parameters in the parental term of the likelihood function are set to 0, but revealed convergence problems when estimating these parental association parameters separately. The former approach is thus recommended with polytomous phenotypes.
journal_name
Stat Appl Genet Mol Biolauthors
Bureau A,Croteau Jdoi
10.1515/sagmb-2016-0035subject
Has Abstractpub_date
2017-03-01 00:00:00pages
75-81issue
1eissn
2194-6302issn
1544-6115pii
/j/sagmb.ahead-of-print/sagmb-2016-0035/sagmb-2016journal_volume
16pub_type
杂志文章abstract::We present a Bayesian hierarchical model for detecting differentially expressed genes using a mixture prior on the parameters representing differential effects. We formulate an easily interpretable 3-component mixture to classify genes as over-expressed, under-expressed and non-differentially expressed, and model gene...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1314
更新日期:2007-01-01 00:00:00
abstract::Gametic models for fitting breeding values at QTL as random effects in outbred populations have become popular because they require few assumptions about the number and distribution of QTL alleles segregating. The covariance matrix of the gametic effects has an inverse that is sparse and can be constructed rapidly by ...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1048
更新日期:2004-01-01 00:00:00
abstract::Integrative analysis of copy number and gene expression data can help in understanding the cis and trans effect of copy number aberrations on transcription levels of genes involved in a pathway. To analyse how these copy number mediated gene-gene interactions differ between groups of samples we propose a new method, n...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2017-0058
更新日期:2018-07-31 00:00:00
abstract::Multi-color optical mapping is a new technique being developed to obtain detailed physical maps (indicating relative positions of various recognition sites) of DNA molecules. We consider a study design in which the data consist of noisy observations of multiple copies of a DNA molecule marked with colors at recognitio...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1266
更新日期:2007-01-01 00:00:00
abstract::Many gene- and pathway-based association tests have been proposed in the literature. Among them, the SKAT is widely used, especially for rare variants association studies. In this paper, we investigate the connection between SKAT and a principal component analysis. This investigation leads to a procedure that encompas...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2016-0061
更新日期:2017-07-26 00:00:00
abstract::Multiple testing procedures are commonly used in gene expression studies for the detection of differential expression, where typically thousands of genes are measured over at least two experimental conditions. Given the need for powerful testing procedures, and the attendant danger of false positives in multiple testi...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1302
更新日期:2007-01-01 00:00:00
abstract::In the exploding field of gene expression techniques such as DNA microarrays, there are still few general probabilistic methods for analysis of variance. Linear models and ANOVA are heavily used tools in many other disciplines of scientific research. The usual F-statistic is unsatisfactory for microarray data, which e...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1125
更新日期:2005-01-01 00:00:00
abstract::We evaluate variable selection by multiple tests controlling the false discovery rate (FDR) to build a linear score for prediction of clinical outcome in high-dimensional data. Quality of prediction is assessed by the receiver operating characteristic curve (ROC) for prediction in independent patients. Thus we try to ...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1462
更新日期:2009-01-01 00:00:00
abstract::Making sound proteomic inferences using ELISA microarray assay requires both an accurate prediction of protein concentration and a credible estimate of its error. We present a method using monotonic spline statistical models (MS), penalized constrained least squares fitting (PCLS) and Monte Carlo simulation (MC) to pr...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1364
更新日期:2008-01-01 00:00:00
abstract::Unraveling interactions among variables such as genetic, clinical, demographic and environmental factors is essential to understand the development of common and complex diseases. To increase the power to detect such variables interactions associated with clinical time-to-events outcomes, we borrowed established conce...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2017-0038
更新日期:2018-02-17 00:00:00
abstract::There has been increasing interest in predicting patients' survival after therapy by investigating gene expression microarray data. In the regression and classification models with high-dimensional genomic data, boosting has been successfully applied to build accurate predictive models and conduct variable selection s...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1550
更新日期:2010-01-01 00:00:00
abstract::Usually, a pedigree is sampled and included in the sample that is analyzed after following a predefined non-random sampling design comprising several specific procedures. To obtain a pedigree analysis result free from the bias caused by the sampling procedures, a correction is applied to the pedigree likelihood. The s...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1003
更新日期:2003-01-01 00:00:00
abstract::Gene microarray technology is often used to compare the expression of thousand of genes in two different cell lines. Typically, one does not expect measurable changes in transcription amounts for a large number of genes; furthermore, the noise level of array experiments is rather high in relation to the available numb...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1132
更新日期:2005-01-01 00:00:00
abstract::We present an approach to association studies involving a dozen or so ;response' variables and a few hundred ;explanatory' variables which emphasizes transparency, simplicity, and protection against spurious results. The methods proposed are largely non-parametric, and they are systematically rounded-off by the Benjam...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1420
更新日期:2009-01-01 00:00:00
abstract::In many population genetic problems, parameter estimation is obstructed by an intractable likelihood function. Therefore, approximate estimation methods have been developed, and with growing computational power, sampling-based methods became popular. However, these methods such as Approximate Bayesian Computation (ABC...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2017-0016
更新日期:2017-11-27 00:00:00
abstract::Germline mosaicism is a genetic condition in which some germ cells of an individual contain a mutation. This condition violates the assumptions underlying classic genetic analysis and may lead to failure of such analysis. In this work we extend the statistical model used for genetic linkage analysis in order to incorp...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1709
更新日期:2011-10-04 00:00:00
abstract::The Dirichlet Process (DP) mixture model has become a popular choice for model-based clustering, largely because it allows the number of clusters to be inferred. The sequential updating and greedy search (SUGS) algorithm (Wang & Dunson, 2011) was proposed as a fast method for performing approximate Bayesian inference ...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2018-0065
更新日期:2019-12-12 00:00:00
abstract::High-throughput sequencing techniques are increasingly affordable and produce massive amounts of data. Together with other high-throughput technologies, such as microarrays, there are an enormous amount of resources in databases. The collection of these valuable data has been routine for more than a decade. Despite di...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2014-0093
更新日期:2015-06-01 00:00:00
abstract::The ENCODE project has funded the generation of a diverse collection of methylation profiles using reduced representation bisulfite sequencing (RRBS) technology, enabling the analysis of epigenetic variation on a genomic scale at single-site resolution. A standard application of RRBS experiments is in the location of ...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2013-0027
更新日期:2013-12-01 00:00:00
abstract::In this study, we propose a novel statistical framework for detecting progressive changes in molecular traits as response to a pathogenic stimulus. In particular, we propose to employ Bayesian hierarchical models to analyse changes in mean level, variance and correlation of metabolic traits in relation to covariates. ...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2013-0041
更新日期:2014-04-01 00:00:00
abstract::The problem of finding periodically expressed genes from time course microarray experiments is at the center of numerous efforts to identify the molecular components of biological clocks. We present a new approach to this problem based on the cyclohedron test, which is a rank test inspired by recent advances in algebr...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1286
更新日期:2007-01-01 00:00:00
abstract::We develop an approach for microarray differential expression analysis, i.e. identifying genes whose expression levels differ between two or more groups. Current approaches to inference rely either on full parametric assumptions or on permutation-based techniques for sampling under the null distribution. In some situa...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1333
更新日期:2008-01-01 00:00:00
abstract::Several important syndromes are caused by deleterious germline mutations of individual genes. In both clinical and research applications it is useful to evaluate the probability that an individual carries an inherited genetic variant of these genes, and to predict the risk of disease for that individual, using informa...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1063
更新日期:2004-01-01 00:00:00
abstract::We address a potential shortcoming of three probabilistic models for detecting interspecific recombination in DNA sequence alignments: the multiple change-point model (MCP) of Suchard et al. (2003), the dual multiple change-point model (DMCP) of Minin et al. (2005), and the phylogenetic factorial hidden Markov model (...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1399
更新日期:2008-01-01 00:00:00
abstract::In recent years, alignment-free methods have been widely applied in comparing genome sequences, as these methods compute efficiently and provide desirable phylogenetic analysis results. These methods have been successfully combined with hierarchical clustering methods for finding phylogenetic trees. However, it may no...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2018-0045
更新日期:2019-02-15 00:00:00
abstract::We are concerned with statistical inference for 2 × C × K contingency tables in the context of genetic case-control association studies. Multivariate methods based on asymptotic Gaussianity of vectors of test statistics require information about the asymptotic correlation structure among these test statistics under th...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2015-0024
更新日期:2015-11-01 00:00:00
abstract::The objective of the present paper is to develop a truly functional Bayesian method specifically designed for time series microarray data. The method allows one to identify differentially expressed genes in a time-course microarray experiment, to rank them and to estimate their expression profiles. Each gene expressio...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1299
更新日期:2007-01-01 00:00:00
abstract::In cellular biology, node-and-edge graph or "network" data collection often uses bait-prey technologies such as co-immunoprecipitation (CoIP). Bait-prey technologies assay relationships or "interactions" between protein pairs, with CoIP specifically measuring protein complex co-membership. Analyses of CoIP data freque...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2015-0007
更新日期:2015-08-01 00:00:00
abstract::Reproducibility of disease signatures and clinical biomarkers in multi-omics disease analysis has been a key challenge due to a multitude of factors. The heterogeneity of the limited sample, various biological factors such as environmental confounders, and the inherent experimental and technical noises, compounded wit...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2018-0039
更新日期:2019-05-11 00:00:00
abstract::In a hidden Markov model, one "estimates" the state of the hidden Markov chain at t by computing via the forwards-backwards algorithm the conditional distribution of the state vector given the observed data. The covariance matrix of this conditional distribution measures the information lost by failure to observe dire...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章,评审
doi:10.2202/1544-6115.1296
更新日期:2007-01-01 00:00:00