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 incorporate germline mosaicism. We develop a likelihood ratio test for detecting whether a genetic trait has been introduced into a pedigree by germline mosaicism. We analyze the statistical properties of this test and evaluate its performance via computer simulations. We demonstrate that genetic linkage analysis has high power to identify linkage in the presence of germline mosaicism when our extended model is used. We further use this extended model to provide solid statistical evidence that the MDN syndrome studied by Genzer-Nir et al. has been introduced by germline mosaicism.
journal_name
Stat Appl Genet Mol Biolauthors
Weissbrod O,Geiger Ddoi
10.2202/1544-6115.1709subject
Has Abstractpub_date
2011-10-04 00:00:00issue
1eissn
2194-6302issn
1544-6115pii
/j/sagmb.2011.10.issue-1/1544-6115.1709/1544-6115.journal_volume
10pub_type
杂志文章abstract::In candidate gene association studies, usually several elementary hypotheses are tested simultaneously using one particular set of data. The data normally consist of partly correlated SNP information. Every SNP can be tested for association with the disease, e.g., using the Cochran-Armitage test for trend. To account ...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1729
更新日期:2011-01-01 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::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::Approaches based upon sequence weights, to construct a position weight matrix of nucleotides from aligned inputs, are popular but little effort has been expended to measure their quality. We derive optimal sequence weights that minimize the sum of the variances of the estimators of base frequency parameters for sequen...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1135
更新日期:2005-01-01 00:00:00
abstract::Various discriminant methods have been applied for classification of tumors based on gene expression profiles, among which the nearest neighbor (NN) method has been reported to perform relatively well. Usually cross-validation (CV) is used to select the neighbor size as well as the number of variables for the NN metho...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1054
更新日期:2004-01-01 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
abstract::Consider the standard multiple testing problem where many hypotheses are to be tested, each hypothesis is associated with a test statistic, and large test statistics provide evidence against the null hypotheses. One proposal to provide probabilistic control of Type-I errors is the use of procedures ensuring that the e...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1148
更新日期:2006-01-01 00:00:00
abstract::In this paper, we address the problem of detecting outlier samples with highly different expression patterns in microarray data. Although outliers are not common, they appear even in widely used benchmark data sets and can negatively affect microarray data analysis. It is important to identify outliers in order to exp...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1426
更新日期:2009-01-01 00:00:00
abstract::Accurately measuring epigenetic marks such as 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) at the single-nucleotide level, requires combining data from DNA processing methods including traditional (BS), oxidative (oxBS) or Tet-Assisted (TAB) bisulfite conversion. We introduce the R package MLML2R, which...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2018-0031
更新日期:2019-01-17 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::Multiple branching trees have been used to model the acquisition of HIV drug resistance mutations, and several different algorithms have been developed to construct the tree set that best describes the data. These algorithms have mainly focused on the structure of the tree set. The focal point of this paper is estimat...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1324
更新日期:2008-01-01 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 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::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::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::We present a weighted-LASSO method to infer the parameters of a first-order vector auto-regressive model that describes time course expression data generated by directed gene-to-gene regulation networks. These networks are assumed to own prior internal structures of connectivity which drive the inference method. This ...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1519
更新日期:2010-01-01 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::Longitudinal genomics data and survival outcome are common in biomedical studies, where the genomics data are often of high dimension. It is of great interest to select informative longitudinal biomarkers (e.g. genes) related to the survival outcome. In this paper, we develop a computationally efficient tool, LCox, fo...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2017-0060
更新日期:2019-02-13 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::Recent analytic and technological breakthroughs have set the stage for genome-wide linkage disequilibrium studies to map disease-susceptibility variants. This paper discusses a probabilistic methodology for making disease-mapping inferences in large-scale case-control genetic studies. The semi-Bayesian approach promot...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1168
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::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::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 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::Likelihood-based cross-validation is a statistical tool for selecting a density estimate based on n i.i.d. observations from the true density among a collection of candidate density estimators. General examples are the selection of a model indexing a maximum likelihood estimator, and the selection of a bandwidth index...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1036
更新日期:2004-01-01 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::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::Combining correlated p-values from multiple hypothesis testing is a most frequently used method for integrating information in genetic and genomic data analysis. However, most existing methods for combining independent p-values from individual component problems into a single unified p-value are unsuitable for the cor...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.1515/sagmb-2019-0057
更新日期:2020-11-06 00:00:00
abstract::In this paper, we explore the use of M-quantile regression and M-quantile coefficients to detect statistical differences between temporal curves that belong to different experimental conditions. In particular, we consider the application of temporal gene expression data. Here, the aim is to detect genes whose temporal...
journal_title:Statistical applications in genetics and molecular biology
pub_type: 杂志文章
doi:10.2202/1544-6115.1452
更新日期:2009-01-01 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