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Statistical Applications in Genetics and Molecular Biology

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https://www.readbyqxmd.com/read/29601301/on-a-mutual-information-estimator-with-exponentially-decaying-bias-by-zhang-and-zheng
#1
Jialin Zhang, Chen Chen
Zhang, Z. and Zheng, L. (2015): "A mutual information estimator with exponentially decaying bias," Stat. Appl. Genet. Mol. Biol., 14, 243-252, proposed a nonparametric estimator of mutual information developed in entropic perspective, and demonstrated that it has much smaller bias than the plugin estimator yet with the same asymptotic normality under certain conditions. However it is incorrectly suggested in their article that the asymptotic normality could be used for testing independence between two random elements on a joint alphabet...
March 30, 2018: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29420308/additive-varying-coefficient-model-for-nonlinear-gene-environment-interactions
#2
Cen Wu, Ping-Shou Zhong, Yuehua Cui
Gene-environment (G×E) interaction plays a pivotal role in understanding the genetic basis of complex disease. When environmental factors are measured continuously, one can assess the genetic sensitivity over different environmental conditions on a disease trait. Motivated by the increasing awareness of gene set based association analysis over single variant based approaches, we proposed an additive varying-coefficient model to jointly model variants in a genetic system. The model allows us to examine how variants in a gene set are moderated by an environment factor to affect a disease phenotype...
February 8, 2018: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29397393/distance-correlation-based-gene-set-analysis-in-longitudinal-studies
#3
Jiehuan Sun, Jose D Herazo-Maya, Xiu Huang, Naftali Kaminski, Hongyu Zhao
Longitudinal gene expression profiles of subjects are collected in some clinical studies to monitor disease progression and understand disease etiology. The identification of gene sets that have coordinated changes with relevant clinical outcomes over time from these data could provide significant insights into the molecular basis of disease progression and lead to better treatments. In this article, we propose a Distance-Correlation based Gene Set Analysis (dcGSA) method for longitudinal gene expression data...
February 5, 2018: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29381476/tests-for-comparison-of-multiple-endpoints-with-application-to-omics-data
#4
Marco Marozzi
In biomedical research, multiple endpoints are commonly analyzed in "omics" fields like genomics, proteomics and metabolomics. Traditional methods designed for low-dimensional data either perform poorly or are not applicable when analyzing high-dimensional data whose dimension is generally similar to, or even much larger than, the number of subjects. The complex biochemical interplay between hundreds (or thousands) of endpoints is reflected by complex dependence relations. The aim of the paper is to propose tests that are very suitable for analyzing omics data because they do not require the normality assumption, are powerful also for small sample sizes, in the presence of complex dependence relations among endpoints, and when the number of endpoints is much larger than the number of subjects...
January 30, 2018: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29453930/ensemble-survival-tree-models-to-reveal-pairwise-interactions-of-variables-with-time-to-events-outcomes-in-low-dimensional-setting
#5
Jean-Eudes Dazard, Hemant Ishwaran, Rajeev Mehlotra, Aaron Weinberg, Peter Zimmerman
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 concepts from random survival forest (RSF) models. We introduce a novel RSF-based pairwise interaction estimator and derive a randomization method with bootstrap confidence intervals for inferring interaction significance...
February 17, 2018: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29166289/a-statistical-method-for-analysing-cospeciation-in-tritrophic-ecology-using-electrical-circuit-theory
#6
Colleen Nooney, Stuart Barber, Arief Gusnanto, Walter R Gilks
We introduce a new method to test efficiently for cospeciation in tritrophic systems. Our method utilises an analogy with electrical circuit theory to reduce higher order systems into bitrophic data sets that retain the information of the original system. We use a sophisticated permutation scheme that weights interactions between two trophic layers based on their connection to the third layer in the system. Our method has several advantages compared to the method of Mramba et al. [Mramba, L. K., S. Barber, K...
November 27, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29140792/a-bayesian-hierarchical-model-for-identifying-significant-polygenic-effects-while-controlling-for-confounding-and-repeated-measures
#7
Christopher McMahan, James Baurley, William Bridges, Chase Joyner, Muhamad Fitra Kacamarga, Robert Lund, Carissa Pardamean, Bens Pardamean
Genomic studies of plants often seek to identify genetic factors associated with desirable traits. The process of evaluating genetic markers one by one (i.e. a marginal analysis) may not identify important polygenic and environmental effects. Further, confounding due to growing conditions/factors and genetic similarities among plant varieties may influence conclusions. When developing new plant varieties to optimize yield or thrive in future adverse conditions (e.g. flood, drought), scientists seek a complete understanding of how the factors influence desirable traits...
November 27, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29095700/approximate-maximum-likelihood-estimation-for-population-genetic-inference
#8
Johanna Bertl, Gregory Ewing, Carolin Kosiol, Andreas Futschik
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) can be inefficient in high-dimensional problems. This led to the development of more sophisticated iterative estimation methods like particle filters. Here, we propose an alternative approach that is based on stochastic approximation...
November 27, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29091583/bayesian-estimation-of-differential-transcript-usage-from-rna-seq-data
#9
Panagiotis Papastamoulis, Magnus Rattray
Next generation sequencing allows the identification of genes consisting of differentially expressed transcripts, a term which usually refers to changes in the overall expression level. A specific type of differential expression is differential transcript usage (DTU) and targets changes in the relative within gene expression of a transcript. The contribution of this paper is to: (a) extend the use of cjBitSeq to the DTU context, a previously introduced Bayesian model which is originally designed for identifying changes in overall expression levels and (b) propose a Bayesian version of DRIMSeq, a frequentist model for inferring DTU...
November 27, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29091582/multivariate-association-between-single-nucleotide-polymorphisms-in-alzgene-linkage-regions-and-structural-changes-in-the-brain-discovery-refinement-and-validation
#10
Elena Szefer, Donghuan Lu, Farouk Nathoo, Mirza Faisal Beg, Jinko Graham
Using publicly-available data from the Alzheimer's Disease Neuroimaging Initiative, we investigate the joint association between single-nucleotide polymorphisms (SNPs) in previously established linkage regions for Alzheimer's disease (AD) and rates of decline in brain structure. In an initial, discovery stage of analysis, we applied a weighted RV test to assess the association between 75,845 SNPs in the Alzgene linkage regions and rates of change in structural MRI measurements for 56 brain regions affected by AD, in 632 subjects...
November 27, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29077555/modifying-samseq-to-account-for-asymmetry-in-the-distribution-of-effect-sizes-when-identifying-differentially-expressed-genes
#11
Ekua Kotoka, Megan Orr
RNA-Seq is a developing technology for generating gene expression data by directly sequencing mRNA molecules in a sample. RNA-Seq data consist of counts of reads recorded to a particular gene that are often used to identify differentially expressed (DE) genes. A common statistical method used to analyze RNA-Seq data is Significance Analysis of Microarray with emphasis on RNA-Seq data (SAMseq). SAMseq is a nonparametric method that uses a resampling technique to account for differences in sequencing depths when identifying DE genes...
November 27, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29055941/a-smoothed-em-algorithm-for-dna-methylation-profiles-from-sequencing-based-methods-in-cell-lines-or-for-a-single-cell-type
#12
Lajmi Lakhal-Chaieb, Celia M T Greenwood, Mohamed Ouhourane, Kaiqiong Zhao, Belkacem Abdous, Karim Oualkacha
We consider the assessment of DNA methylation profiles for sequencing-derived data from a single cell type or from cell lines. We derive a kernel smoothed EM-algorithm, capable of analyzing an entire chromosome at once, and to simultaneously correct for experimental errors arising from either the pre-treatment steps or from the sequencing stage and to take into account spatial correlations between DNA methylation profiles at neighbouring CpG sites. The outcomes of our algorithm are then used to (i) call the true methylation status at each CpG site, (ii) provide accurate smoothed estimates of DNA methylation levels, and (iii) detect differentially methylated regions...
November 27, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28862994/fc1000-normalized-gene-expression-changes-of-systematically-perturbed-human-cells
#13
Ingrid M Lönnstedt, Sven Nelander
The systematic study of transcriptional responses to genetic and chemical perturbations in human cells is still in its early stages. The largest available dataset to date is the newly released L1000 compendium. With its 1.3 million gene expression profiles of treated human cells it offers many opportunities for biomedical data mining, but also data normalization challenges of new dimensions. We developed a novel and practical approach to obtain accurate estimates of fold change response profiles from L1000, based on the RUV (Remove Unwanted Variation) statistical framework...
September 26, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28862993/a-statistical-test-for-detecting-parent-of-origin-effects-when-parental-information-is-missing
#14
Chiara Sacco, Cinzia Viroli, Mario Falchi
Genomic imprinting is an epigenetic mechanism that leads to differential contributions of maternal and paternal alleles to offspring gene expression in a parent-of-origin manner. We propose a novel test for detecting the parent-of-origin effects (POEs) in genome wide genotype data from related individuals (twins) when the parental origin cannot be inferred. The proposed method exploits a finite mixture of linear mixed models: the key idea is that in the case of POEs the population can be clustered in two different groups in which the reference allele is inherited by a different parent...
September 26, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28862992/bayesian-comparison-of-protein-structures-using-partial-procrustes-distance
#15
Nasim Ejlali, Mohammad Reza Faghihi, Mehdi Sadeghi
An important topic in bioinformatics is the protein structure alignment. Some statistical methods have been proposed for this problem, but most of them align two protein structures based on the global geometric information without considering the effect of neighbourhood in the structures. In this paper, we provide a Bayesian model to align protein structures, by considering the effect of both local and global geometric information of protein structures. Local geometric information is incorporated to the model through the partial Procrustes distance of small substructures...
September 26, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28862991/confidence-intervals-for-heritability-via-haseman-elston-regression
#16
Tamar Sofer
Heritability is the proportion of phenotypic variance in a population that is attributable to individual genotypes. Heritability is considered an important measure in both evolutionary biology and in medicine, and is routinely estimated and reported in genetic epidemiology studies. In population-based genome-wide association studies (GWAS), mixed models are used to estimate variance components, from which a heritability estimate is obtained. The estimated heritability is the proportion of the model's total variance that is due to the genetic relatedness matrix (kinship measured from genotypes)...
September 26, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28734115/regularized-estimation-in-sparse-high-dimensional-multivariate-regression-with-application-to-a-dna-methylation-study
#17
Haixiang Zhang, Yinan Zheng, Grace Yoon, Zhou Zhang, Tao Gao, Brian Joyce, Wei Zhang, Joel Schwartz, Pantel Vokonas, Elena Colicino, Andrea Baccarelli, Lifang Hou, Lei Liu
In this article, we consider variable selection for correlated high dimensional DNA methylation markers as multivariate outcomes. A novel weighted square-root LASSO procedure is proposed to estimate the regression coefficient matrix. A key feature of this method is tuning-insensitivity, which greatly simplifies the computation by obviating cross validation for penalty parameter selection. A precision matrix obtained via the constrained ℓ1 minimization method is used to account for the within-subject correlation among multivariate outcomes...
July 26, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28727569/comparing-the-performance-of-linear-and-nonlinear-principal-components-in-the-context-of-high-dimensional-genomic-data-integration
#18
Shofiqul Islam, Sonia Anand, Jemila Hamid, Lehana Thabane, Joseph Beyene
Linear principal component analysis (PCA) is a widely used approach to reduce the dimension of gene or miRNA expression data sets. This method relies on the linearity assumption, which often fails to capture the patterns and relationships inherent in the data. Thus, a nonlinear approach such as kernel PCA might be optimal. We develop a copula-based simulation algorithm that takes into account the degree of dependence and nonlinearity observed in these data sets. Using this algorithm, we conduct an extensive simulation to compare the performance of linear and kernel principal component analysis methods towards data integration and death classification...
July 26, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28723613/mixture-model-based-association-analysis-with-case-control-data-in-genome-wide-association-studies
#19
Fadhaa Ali, Jian Zhang
Multilocus haplotype analysis of candidate variants with genome wide association studies (GWAS) data may provide evidence of association with disease, even when the individual loci themselves do not. Unfortunately, when a large number of candidate variants are investigated, identifying risk haplotypes can be very difficult. To meet the challenge, a number of approaches have been put forward in recent years. However, most of them are not directly linked to the disease-penetrances of haplotypes and thus may not be efficient...
July 26, 2017: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28672760/genetic-association-test-based-on-principal-component-analysis
#20
Zhongxue Chen, Shizhong Han, Kai Wang
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 encompasses SKAT as a special case. Through simulation studies and real data applications, we compare the proposed method with some existing tests.
July 26, 2017: Statistical Applications in Genetics and Molecular Biology
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