scholarly journals GBAT: a gene-based association method for robust trans-gene regulation detection

2018 ◽  
Author(s):  
Xuanyao Liu ◽  
Joel A Mefford ◽  
Andrew Dahl ◽  
Meena Subramaniam ◽  
Alexis Battle ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Multiple Testing ◽  
Real Data ◽  
Read Mapping ◽  
Robust Detection ◽  
Association Method ◽  
Trans Gene

AbstractIdentification of trans-eQTLs has been limited by a heavy multiple testing burden, read-mapping biases, and hidden confounders. To address these issues, we developed GBAT, a powerful gene-based method that allows robust detection of trans gene regulation. Using simulated and real data, we show that GBAT drastically increases detection of trans-gene regulation over standard trans-eQTL analyses.

scholarly journals GBAT: a gene-based association test for robust detection of trans-gene regulation

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuanyao Liu ◽  
Joel A. Mefford ◽  
Andrew Dahl ◽  
Yuan He ◽  
Meena Subramaniam ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Association Test ◽  
Robust Detection ◽  
Trans Gene

scholarly journals Chicdiff: a computational pipeline for detecting differential chromosomal interactions in Capture Hi-C data

2019 ◽  
Vol 35 (22) ◽  
pp. 4764-4766 ◽  
Author(s):  
Jonathan Cairns ◽  
William R Orchard ◽  
Valeriya Malysheva ◽  
Mikhail Spivakov
Keyword(s):  
Multiple Testing ◽  
Positive Association ◽  
R Package ◽  
Supplementary Information ◽  
Gene Promoters ◽  
Robust Detection ◽  
Testing Procedures ◽  
Multiple Testing Procedures ◽  
Powerful Approach ◽  
Cell Type Specific

Abstract Summary Capture Hi-C is a powerful approach for detecting chromosomal interactions involving, at least on one end, DNA regions of interest, such as gene promoters. We present Chicdiff, an R package for robust detection of differential interactions in Capture Hi-C data. Chicdiff enhances a state-of-the-art differential testing approach for count data with bespoke normalization and multiple testing procedures that account for specific statistical properties of Capture Hi-C. We validate Chicdiff on published Promoter Capture Hi-C data in human Monocytes and CD4+ T cells, identifying multitudes of cell type-specific interactions, and confirming the overall positive association between promoter interactions and gene expression. Availability and implementation Chicdiff is implemented as an R package that is publicly available at https://github.com/RegulatoryGenomicsGroup/chicdiff. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Joint variable selection and network modeling for detecting eQTLs

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Xuan Cao ◽  
Lili Ding ◽  
Tesfaye B. Mersha
Keyword(s):  
Variable Selection ◽  
Multiple Testing ◽  
Bayes Factor ◽  
Graph Model ◽  
Real Data ◽  
Bayesian Regression ◽  
Joint Estimation ◽  
Eqtl Analysis ◽  
Multiple Testing Correction ◽  
Joint Variable

AbstractIn this study, we conduct a comparison of three most recent statistical methods for joint variable selection and covariance estimation with application of detecting expression quantitative trait loci (eQTL) and gene network estimation, and introduce a new hierarchical Bayesian method to be included in the comparison. Unlike the traditional univariate regression approach in eQTL, all four methods correlate phenotypes and genotypes by multivariate regression models that incorporate the dependence information among phenotypes, and use Bayesian multiplicity adjustment to avoid multiple testing burdens raised by traditional multiple testing correction methods. We presented the performance of three methods (MSSL – Multivariate Spike and Slab Lasso, SSUR – Sparse Seemingly Unrelated Bayesian Regression, and OBFBF – Objective Bayes Fractional Bayes Factor), along with the proposed, JDAG (Joint estimation via a Gaussian Directed Acyclic Graph model) method through simulation experiments, and publicly available HapMap real data, taking asthma as an example. Compared with existing methods, JDAG identified networks with higher sensitivity and specificity under row-wise sparse settings. JDAG requires less execution in small-to-moderate dimensions, but is not currently applicable to high dimensional data. The eQTL analysis in asthma data showed a number of known gene regulations such as STARD3, IKZF3 and PGAP3, all reported in asthma studies. The code of the proposed method is freely available at GitHub (https://github.com/xuan-cao/Joint-estimation-for-eQTL).

scholarly journals Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases

Science ◽  
2016 ◽  
Vol 353 (6301) ◽  
pp. 827-830 ◽  
Author(s):  
O. Franzen ◽  
R. Ermel ◽  
A. Cohain ◽  
N. K. Akers ◽  
A. Di Narzo ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Cardiometabolic Risk ◽  
Cis And Trans ◽  
Trans Gene

scholarly journals Mixture model-based association analysis with case-control data in genome wide association studies

2017 ◽  
Vol 16 (3) ◽  
Author(s):  
Fadhaa Ali ◽  
Jian Zhang
Keyword(s):  
Mixture Model ◽  
Multiple Testing ◽  
Hypothesis Test ◽  
Association Studies ◽  
Real Data ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Model Based ◽  
Genome Wide ◽  
The Individual

AbstractMultilocus 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. To fill this gap, we propose a mixture model-based approach for detecting risk haplotypes. Under the mixture model, haplotypes are clustered directly according to their estimated disease penetrances. A theoretical justification of the above model is provided. Furthermore, we introduce a hypothesis test for haplotype inheritance patterns which underpin this model. The performance of the proposed approach is evaluated by simulations and real data analysis. The results show that the proposed approach outperforms an existing multiple testing method.

scholarly journals Gene regulation inference from single-cell RNA-seq data with linear differential equations and velocity inference

2018 ◽  
Author(s):  
Pierre-Cyril Aubin-Frankowski ◽  
Jean-Philippe Vert
Keyword(s):  
Gene Regulation ◽  
Single Cell ◽  
De Novo ◽  
State Of The Art ◽  
Real Data ◽  
Biological Processes ◽  
Rna Seq ◽  
Cell Cycles ◽  
Linear Differential ◽  
Cell Trajectories

AbstractSingle-cell RNA sequencing (scRNA-seq) offers new possibilities to infer gene regulation networks (GRN) for biological processes involving a notion of time, such as cell differentiation or cell cycles. It also raises many challenges due to the destructive measurements inherent to the technology. In this work we propose a new method named GRISLI for de novo GRN inference from scRNA-seq data. GRISLI infers a velocity vector field in the space of scRNA-seq data from profiles of individual data, and models the dynamics of cell trajectories with a linear ordinary differential equation to reconstruct the underlying GRN with a sparse regression procedure. We show on real data that GRISLI outperforms a recently proposed state-of-the-art method for GRN reconstruction from scRNA-seq data.

scholarly journals Spatial Organization of the Gene Regulatory Program: An Information Theoretical Approach to Breast Cancer Transcriptomics

Entropy ◽  
2019 ◽  
Vol 21 (2) ◽  
pp. 195 ◽  
Author(s):  
Guillermo de Anda-Jáuregui ◽  
Jesús Espinal-Enriquez ◽  
Enrique Hernández-Lemus
Keyword(s):  
Breast Cancer ◽  
Gene Regulation ◽  
Spatial Organization ◽  
Spatial Relationship ◽  
Information Theoretic ◽  
Gene Regulatory ◽  
Trans Regulation ◽  
Cis And Trans ◽  
Biological State ◽  
Trans Gene

Gene regulation may be studied from an information-theoretic perspective. Gene regulatory programs are representations of the complete regulatory phenomenon associated to each biological state. In diseases such as cancer, these programs exhibit major alterations, which have been associated with the spatial organization of the genome into chromosomes. In this work, we analyze intrachromosomal, or cis-, and interchromosomal, or trans-gene regulatory programs in order to assess the differences that arise in the context of breast cancer. We find that using information theoretic approaches, it is possible to differentiate cis-and trans-regulatory programs in terms of the changes that they exhibit in the breast cancer context, indicating that in breast cancer there is a loss of trans-regulation. Finally, we use these programs to reconstruct a possible spatial relationship between chromosomes.

scholarly journals Evaluation of Second-Level Inference in fMRI Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Sanne P. Roels ◽  
Tom Loeys ◽  
Beatrijs Moerkerke
Keyword(s):  
Error Rate ◽  
Cluster Size ◽  
Multiple Testing ◽  
Real Data ◽  
False Positives ◽  
Familywise Error Rate ◽  
False Negatives ◽  
Step Procedure ◽  
Fmri Analysis ◽  
The Impact

We investigate the impact of decisions in the second-level (i.e., over subjects) inferential process in functional magnetic resonance imaging on (1) the balance between false positives and false negatives and on (2) the data-analytical stability, both proxies for the reproducibility of results. Second-level analysis based on a mass univariate approach typically consists of 3 phases. First, one proceeds via a general linear model for a test image that consists of pooled information from different subjects. We evaluate models that take into account first-level (within-subjects) variability and models that do not take into account this variability. Second, one proceeds via inference based on parametrical assumptions or via permutation-based inference. Third, we evaluate 3 commonly used procedures to address the multiple testing problem: familywise error rate correction, False Discovery Rate (FDR) correction, and a two-step procedure with minimal cluster size. Based on a simulation study and real data we find that the two-step procedure with minimal cluster size results in most stable results, followed by the familywise error rate correction. The FDR results in most variable results, for both permutation-based inference and parametrical inference. Modeling the subject-specific variability yields a better balance between false positives and false negatives when using parametric inference.

Evolutionary changes in cis and trans gene regulation

Nature ◽  
2004 ◽  
Vol 430 (6995) ◽  
pp. 85-88 ◽  
Author(s):  
Patricia J. Wittkopp ◽  
Belinda K. Haerum ◽  
Andrew G. Clark
Keyword(s):  
Gene Regulation ◽  
Evolutionary Changes ◽  
Cis And Trans ◽  
In Cis ◽  
Trans Gene
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