scholarly journals Two-Step Mixed Model Approach to Analyzing Differential Alternative RNA Splicing

2020 ◽  
Author(s):  
Li Luo ◽  
Huining Kang ◽  
Xichen Li ◽  
Scott A. Ness ◽  
Christine A. Stidley
Keyword(s):  
Rna Splicing ◽  
Statistical Power ◽  
Mixed Model ◽  
Differentially Expressed ◽  
Screening Tests ◽  
Dimensional Structure ◽  
Mixed Model Approach ◽  
Testing Stage ◽  
Gene Level ◽  
Whole Transcriptome

AbstractChanges in gene expression can correlate with poor disease outcomes in two ways: through changes in relative transcript levels or through alternative RNA splicing leading to changes in relative abundance of individual transcript isoforms. The objective of this research is to develop new statistical methods in detecting and analyzing both differentially expressed and spliced isoforms, which appropriately account for the dependence between isoforms and multiple testing corrections for the multi-dimensional structure of at both the gene- and isoform-level. We developed a linear mixed effects model-based approach for analyzing the complex alternative RNA splicing regulation patterns detected by whole-transcriptome RNA-sequencing technologies. This approach thoroughly characterizes and differentiates three types of genes related to alternative RNA splicing events with distinct differential expression/splicing patterns. We applied the concept of appropriately controlling for the gene-level overall false discovery rate (OFDR) in this multi-dimensional alternative RNA splicing analysis utilizing a two-step hierarchical hypothesis testing framework. In the initial screening test we identify genes that have differentially expressed or spliced isoforms; in the subsequent confirmatory testing stage we examine only the isoforms for genes that have passed the screening tests. Comparisons with other methods through application to a whole transcriptome RNA-Seq study of adenoid cystic carcinoma and extensive simulation studies have demonstrated the advantages and improved performances of our method. Our proposed method appropriately controls the gene-level OFDR, maintains statistical power, and is flexible to incorporate advanced experimental designs.

scholarly journals Two-step mixed model approach to analyzing differential alternative RNA splicing

PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0232646
Author(s):  
Li Luo ◽  
Huining Kang ◽  
Xichen Li ◽  
Scott A. Ness ◽  
Christine A. Stidley
Keyword(s):  
Rna Splicing ◽  
Mixed Model ◽  
Mixed Model Approach ◽  
Model Approach

Power of Modified Brown-Forsythe and Mixed-Model Approaches in Split-Plot Designs

Methodology ◽  
2017 ◽  
Vol 13 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Pablo Livacic-Rojas ◽  
Guillermo Vallejo ◽  
Paula Fernández ◽  
Ellián Tuero-Herrero
Keyword(s):  
Repeated Measures ◽  
Statistical Power ◽  
Mixed Model ◽  
Covariance Structure ◽  
Simulation Method ◽  
Future Research ◽  
Repeated Measures Design ◽  
Fixed And Random Effects ◽  
Split Plot ◽  
High Level

Abstract. Low precision of the inferences of data analyzed with univariate or multivariate models of the Analysis of Variance (ANOVA) in repeated-measures design is associated to the absence of normality distribution of data, nonspherical covariance structures and free variation of the variance and covariance, the lack of knowledge of the error structure underlying the data, and the wrong choice of covariance structure from different selectors. In this study, levels of statistical power presented the Modified Brown Forsythe (MBF) and two procedures with the Mixed-Model Approaches (the Akaike’s Criterion, the Correctly Identified Model [CIM]) are compared. The data were analyzed using Monte Carlo simulation method with the statistical package SAS 9.2, a split-plot design, and considering six manipulated variables. The results show that the procedures exhibit high statistical power levels for within and interactional effects, and moderate and low levels for the between-groups effects under the different conditions analyzed. For the latter, only the Modified Brown Forsythe shows high level of power mainly for groups with 30 cases and Unstructured (UN) and Autoregressive Heterogeneity (ARH) matrices. For this reason, we recommend using this procedure since it exhibits higher levels of power for all effects and does not require a matrix type that underlies the structure of the data. Future research needs to be done in order to compare the power with corrected selectors using single-level and multilevel designs for fixed and random effects.

scholarly journals Estimating the effective sample size in association studies of quantitative traits

2021 ◽  
Author(s):  
Andrey Ziyatdinov ◽  
Jihye Kim ◽  
Dmitry Prokopenko ◽  
Florian Privé ◽  
Fabien Laporte ◽  
...  
Keyword(s):  
Statistical Power ◽  
Quantitative Traits ◽  
Mixed Model ◽  
Association Studies ◽  
Effective Sample Size ◽  
Environment Interaction ◽  
Uk Biobank ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
The Uk

Abstract The effective sample size (ESS) is a metric used to summarize in a single term the amount of correlation in a sample. It is of particular interest when predicting the statistical power of genome-wide association studies (GWAS) based on linear mixed models. Here, we introduce an analytical form of the ESS for mixed-model GWAS of quantitative traits and relate it to empirical estimators recently proposed. Using our framework, we derived approximations of the ESS for analyses of related and unrelated samples and for both marginal genetic and gene-environment interaction tests. We conducted simulations to validate our approximations and to provide a quantitative perspective on the statistical power of various scenarios, including power loss due to family relatedness and power gains due to conditioning on the polygenic signal. Our analyses also demonstrate that the power of gene-environment interaction GWAS in related individuals strongly depends on the family structure and exposure distribution. Finally, we performed a series of mixed-model GWAS on data from the UK Biobank and confirmed the simulation results. We notably found that the expected power drop due to family relatedness in the UK Biobank is negligible.

scholarly journals A Fumonisin Prevention Tool for Targeting and Ranking Agroclimatic Conditions Favoring Exposure in French Maize-Growing Areas

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 214
Author(s):  
Agathe Roucou ◽  
Christophe Bergez ◽  
Benoît Méléard ◽  
Béatrice Orlando
Keyword(s):  
Mixed Model ◽  
Linear Mixed Model ◽  
Fusarium Verticillioides ◽  
Agricultural Practices ◽  
Climatic Conditions ◽  
Agricultural Cooperatives ◽  
Mixed Model Approach ◽  
Food And Feed ◽  
Model Approach

The levels of fumonisins (FUMO)—mycotoxins produced by Fusarium verticillioides—in maize for food and feed are subject to European Union regulations. Compliance with the regulations requires the targeting of, among others, the agroclimatic factors influencing fungal contamination and FUMO production. Arvalis-Institut du végétal has created a national, multiyear database for maize, based on field survey data collected since 2003. This database contains information about agricultural practices, climatic conditions and FUMO concentrations at harvest for 738 maize fields distributed throughout French maize-growing regions. A linear mixed model approach highlights the presence of borers and the use of a late variety, high temperatures in July and October, and a water deficit during the maize cycle as creating conditions favoring maize contamination with Fusarium verticillioides. It is thus possible to target a combination of risk factors, consisting of this climatic sequence associated with agricultural practices of interest. The effects of the various possible agroclimatic combinations can be compared, grouped and classified as promoting very low to high FUMO concentrations, possibly exceeding the regulatory threshold. These findings should facilitate the creation of a national, informative and easy-to-use prevention tool for producers and agricultural cooperatives to manage the sanitary quality of their harvest.

scholarly journals Male and female fertility and hatchability in chickens: a longitudinal mixed model approach

2004 ◽  
Vol 83 (8) ◽  
pp. 1253-1259 ◽  
Author(s):  
R.L. Sapp ◽  
R. Rekaya ◽  
I. Misztal ◽  
T. Wing
Keyword(s):  
Mixed Model ◽  
Female Fertility ◽  
Male And Female ◽  
Mixed Model Approach ◽  
Model Approach

Effects of a dance program on psychophysiological variables in hospitalized patients with depression: A mixed model approach

2021 ◽  
pp. 101857
Author(s):  
Karen Melissa Polanco Zuleta ◽  
Marina Medina-Corrales ◽  
Franciso Javier Mendoza-Farías ◽  
Claudia Cristina Santos Lozano ◽  
José Tristán ◽  
...  
Keyword(s):  
Mixed Model ◽  
Hospitalized Patients ◽  
Mixed Model Approach ◽  
Model Approach

scholarly journals Coex-Rank: An approach incorporating co-expression information for combined analysis of microarray data

2012 ◽  
Vol 9 (1) ◽  
pp. 32-43 ◽  
Author(s):  
Jinlu Cai ◽  
Henry L. Keen ◽  
Curt D. Sigmund ◽  
Thomas L. Casavant
Keyword(s):  
Microarray Data ◽  
Statistical Power ◽  
Meta Analysis ◽  
Rank Aggregation ◽  
Microarray Data Analysis ◽  
Combined Approach ◽  
Linear Modeling ◽  
Modeling Process ◽  
Genome Wide ◽  
Gene Level

Summary Microarrays have been widely used to study differential gene expression at the genomic level. They can also provide genome-wide co-expression information. Biologically related datasets from independent studies are publicly available, which requires robust combined approaches for integration and validation. Previously, meta-analysis has been adopted to solve this problem.As an alternative to meta-analysis, for microarray data with high similarity in biological experimental design, a more direct combined approach is possible. Gene-level normalization across datasets is motivated by the different scale and distribution of data due to separate origins. However, there has been limited discussion about this point in the past. Here we describe a combined approach for microarray analysis, including gene-level normalization and Coex-Rank approach. After normalization, a linear modeling process is used to identify lists of differentially expressed genes. The Coex-Rank approach incorporates co-expression information into a rank-aggregation procedure. We applied this computational approach to our data, which illustrated an improvement in statistical power and a complementary advantage of the Coex-Rank approach from a biological perspective.Our combined approach for microarray data analysis (Coex-rank) is based on normalization, which is naturally driven. The Coex-rank process not only takes advantage of merging the power of multiple methods regarding normalization but also assists in the discovery of functional clusters of genes.

scholarly journals Optimal models in the yield analysis of new flax cultivars

2018 ◽  
Vol 98 (4) ◽  
pp. 897-907
Author(s):  
Gaofeng Jia ◽  
Helen M. Booker
Keyword(s):  
Mixed Models ◽  
Statistical Power ◽  
Mixed Model ◽  
Trial Data ◽  
Residual Error ◽  
Yield Data ◽  
Symmetry Model ◽  
Compound Symmetry ◽  
Future Data ◽  
Variety Performance

Multi-environment trials are conducted to evaluate the performance of cultivars. In a combined analysis, the mixed model is superior to an analysis of variance for evaluating and comparing cultivars and dealing with an unbalanced data structure. This study seeks to identify the optimal models using the Saskatchewan Variety Performance Group post-registration regional trial data for flax. Yield data were collected for 15 entries in post-registration tests conducted in Saskatchewan from 2007 to 2016 (except 2011) and 16 mixed models with homogeneous or heterogeneous residual errors were compared. A compound symmetry model with heterogeneous residual error (CSR) had the best fit, with a normal distribution of residuals and a mean of zero fitted to the trial data for each year. The compound symmetry model with homogeneous residual error (CS) and a model extending the CSR to higher dimensions (DIAGR) were the next best models in most cases. Five hundred random samples from a two-stage sampling method were produced to determine the optimal models suitable for various environments. The CSR model was superior to other models for 396 out of 500 samples (79.2%). The top three models, CSR, CS, and DIAGR, had higher statistical power and could be used to access the yield stability of the new flax cultivars. Optimal mixed models are recommended for future data analysis of new flax cultivars in regional tests.

Sign in / Sign up

Export Citation Format

Share Document