Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

False discovery control for penalized variable selections with high-dimensional covariates.

ABSTRACT: Modern bio-technologies have produced a vast amount of high-throughput data with the number of predictors much exceeding the sample size. Penalized variable selection has emerged as a powerful and efficient dimension reduction tool. However, control of false discoveries (i.e. inclusion of irrelevant variables) for penalized high-dimensional variable selection presents serious challenges. To effectively control the fraction of false discoveries for penalized variable selections, we propose a false discovery controlling procedure. The proposed method is general and flexible, and can work with a broad class of variable selection algorithms, not only for linear regressions, but also for generalized linear models and survival analysis.

SUBMITTER: He K

PROVIDER: S-EPMC6450074 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

False discovery control for penalized variable selections with high-dimensional covariates.

He Kevin K Zhou Xiang X Jiang Hui H Wen Xiaoquan X Li Yi Y

Statistical applications in genetics and molecular biology 20181215 6

Modern bio-technologies have produced a vast amount of high-throughput data with the number of predictors much exceeding the sample size. Penalized variable selection has emerged as a powerful and efficient dimension reduction tool. However, control of false discoveries (i.e. inclusion of irrelevant variables) for penalized high-dimensional variable selection presents serious challenges. To effectively control the fraction of false discoveries for penalized variable selections, we propose a fals ...[more]

PMID: 30864387

Similar Datasets

False discovery rate control for high dimensional networks of quantile associations conditioning on covariates.

Project description:Motivated by gene coexpression pattern analysis, we propose a novel sample quantile contingency (SQUAC) statistic to infer quantile associations conditioning on covariates. It features enhanced flexibility in handling variables with both arbitrary distributions and complex association patterns conditioning on covariates. We first derive its asymptotic null distribution, and then develop a multiple-testing procedure based on the SQUAC statistic to test simultaneously the independence between one pair of variables conditioning on covariates for all p(p-1)/2 pairs. Here, p is the length of the outcomes and could exceed the sample size. The testing procedure does not require resampling or perturbation and thus is computationally efficient. We prove by theory and numerical experiments that this testing method asymptotically controls the false discovery rate. It outperforms all alternative methods when the complex association patterns exist. Applied to a gastric cancer data set, this testing method successfully inferred the gene coexpression networks of early and late stage patients. It identified more changes in the networks which are associated with cancer survivals. We extend our method to the case that both the length of the outcomes and the length of covariates exceed the sample size, and show that the asymptotic theory still holds.

| S-EPMC6497089 | biostudies-literature

Component-wise gradient boosting and false discovery control in survival analysis with high-dimensional covariates.

Project description:MOTIVATION:Technological advances that allow routine identification of high-dimensional risk factors have led to high demand for statistical techniques that enable full utilization of these rich sources of information for genetics studies. Variable selection for censored outcome data as well as control of false discoveries (i.e. inclusion of irrelevant variables) in the presence of high-dimensional predictors present serious challenges. This article develops a computationally feasible method based on boosting and stability selection. Specifically, we modified the component-wise gradient boosting to improve the computational feasibility and introduced random permutation in stability selection for controlling false discoveries. RESULTS:We have proposed a high-dimensional variable selection method by incorporating stability selection to control false discovery. Comparisons between the proposed method and the commonly used univariate and Lasso approaches for variable selection reveal that the proposed method yields fewer false discoveries. The proposed method is applied to study the associations of 2339 common single-nucleotide polymorphisms (SNPs) with overall survival among cutaneous melanoma (CM) patients. The results have confirmed that BRCA2 pathway SNPs are likely to be associated with overall survival, as reported by previous literature. Moreover, we have identified several new Fanconi anemia (FA) pathway SNPs that are likely to modulate survival of CM patients. AVAILABILITY AND IMPLEMENTATION:The related source code and documents are freely available at https://sites.google.com/site/bestumich/issues. CONTACT:yili@umich.edu.

| S-EPMC4757968 | biostudies-literature

Consistent high-dimensional Bayesian variable selection via penalized credible regions.

Project description:For high-dimensional data, particularly when the number of predictors greatly exceeds the sample size, selection of relevant predictors for regression is a challenging problem. Methods such as sure screening, forward selection, or penalized regressions are commonly used. Bayesian variable selection methods place prior distributions on the parameters along with a prior over model space, or equivalently, a mixture prior on the parameters having mass at zero. Since exhaustive enumeration is not feasible, posterior model probabilities are often obtained via long MCMC runs. The chosen model can depend heavily on various choices for priors and also posterior thresholds. Alternatively, we propose a conjugate prior only on the full model parameters and use sparse solutions within posterior credible regions to perform selection. These posterior credible regions often have closed-form representations, and it is shown that these sparse solutions can be computed via existing algorithms. The approach is shown to outperform common methods in the high-dimensional setting, particularly under correlation. By searching for a sparse solution within a joint credible region, consistent model selection is established. Furthermore, it is shown that, under certain conditions, the use of marginal credible intervals can give consistent selection up to the case where the dimension grows exponentially in the sample size. The proposed approach successfully accomplishes variable selection in the high-dimensional setting, while avoiding pitfalls that plague typical Bayesian variable selection methods.

| S-EPMC3587767 | biostudies-literature

Joint testing and false discovery rate control in high-dimensional multivariate regression.

Project description:Multivariate regression with high-dimensional covariates has many applications in genomic and genetic research, in which some covariates are expected to be associated with multiple responses. This paper considers joint testing for regression coefficients over multiple responses and develops simultaneous testing methods with false discovery rate control. The test statistic is based on inverse regression and bias-corrected group lasso estimates of the regression coefficients and is shown to have an asymptotic chi-squared null distribution. A row-wise multiple testing procedure is developed to identify the covariates associated with the responses. The procedure is shown to control the false discovery proportion and false discovery rate at a prespecified level asymptotically. Simulations demonstrate the gain in power, relative to entrywise testing, in detecting the covariates associated with the responses. The test is applied to an ovarian cancer dataset to identify the microRNA regulators that regulate protein expression.

| S-EPMC6374004 | biostudies-literature

Accurate error control in high-dimensional association testing using conditional false discovery rates.

Project description:High-dimensional hypothesis testing is ubiquitous in the biomedical sciences, and informative covariates may be employed to improve power. The conditional false discovery rate (cFDR) is a widely used approach suited to the setting where the covariate is a set of p-values for the equivalent hypotheses for a second trait. Although related to the Benjamini-Hochberg procedure, it does not permit any easy control of type-1 error rate and existing methods are over-conservative. We propose a new method for type-1 error rate control based on identifying mappings from the unit square to the unit interval defined by the estimated cFDR and splitting observations so that each map is independent of the observations it is used to test. We also propose an adjustment to the existing cFDR estimator which further improves power. We show by simulation that the new method more than doubles potential improvement in power over unconditional analyses compared to existing methods. We demonstrate our method on transcriptome-wide association studies and show that the method can be used in an iterative way, enabling the use of multiple covariates successively. Our methods substantially improve the power and applicability of cFDR analysis.

| S-EPMC7612315 | biostudies-literature

Penalized Composite Quasi-Likelihood for Ultrahigh-Dimensional Variable Selection.

Project description:In high-dimensional model selection problems, penalized least-square approaches have been extensively used. This paper addresses the question of both robustness and efficiency of penalized model selection methods, and proposes a data-driven weighted linear combination of convex loss functions, together with weighted L(1)-penalty. It is completely data-adaptive and does not require prior knowledge of the error distribution. The weighted L(1)-penalty is used both to ensure the convexity of the penalty term and to ameliorate the bias caused by the L(1)-penalty. In the setting with dimensionality much larger than the sample size, we establish a strong oracle property of the proposed method that possesses both the model selection consistency and estimation efficiency for the true non-zero coefficients. As specific examples, we introduce a robust method of composite L1-L2, and optimal composite quantile method and evaluate their performance in both simulated and real data examples.

| S-EPMC3094588 | biostudies-literature

High Dimensional Variable Selection with Error Control.

Project description:Background. The iterative sure independence screening (ISIS) is a popular method in selecting important variables while maintaining most of the informative variables relevant to the outcome in high throughput data. However, it not only is computationally intensive but also may cause high false discovery rate (FDR). We propose to use the FDR as a screening method to reduce the high dimension to a lower dimension as well as controlling the FDR with three popular variable selection methods: LASSO, SCAD, and MCP. Method. The three methods with the proposed screenings were applied to prostate cancer data with presence of metastasis as the outcome. Results. Simulations showed that the three variable selection methods with the proposed screenings controlled the predefined FDR and produced high area under the receiver operating characteristic curve (AUROC) scores. In applying these methods to the prostate cancer example, LASSO and MCP selected 12 and 8 genes and produced AUROC scores of 0.746 and 0.764, respectively. Conclusions. We demonstrated that the variable selection methods with the sequential use of FDR and ISIS not only controlled the predefined FDR in the final models but also had relatively high AUROC scores.

| S-EPMC5002494 | biostudies-literature

A direct approach to estimating false discovery rates conditional on covariates.

Project description:Modern scientific studies from many diverse areas of research abound with multiple hypothesis testing concerns. The false discovery rate (FDR) is one of the most commonly used approaches for measuring and controlling error rates when performing multiple tests. Adaptive FDRs rely on an estimate of the proportion of null hypotheses among all the hypotheses being tested. This proportion is typically estimated once for each collection of hypotheses. Here, we propose a regression framework to estimate the proportion of null hypotheses conditional on observed covariates. This may then be used as a multiplication factor with the Benjamini-Hochberg adjusted p-values, leading to a plug-in FDR estimator. We apply our method to a genome-wise association meta-analysis for body mass index. In our framework, we are able to use the sample sizes for the individual genomic loci and the minor allele frequencies as covariates. We further evaluate our approach via a number of simulation scenarios. We provide an implementation of this novel method for estimating the proportion of null hypotheses in a regression framework as part of the Bioconductor package swfdr.

| S-EPMC6292380 | biostudies-literature

Penalized logistic regression for high-dimensional DNA methylation data with case-control studies.

Project description:MotivationDNA methylation is a molecular modification of DNA that plays crucial roles in regulation of gene expression. Particularly, CpG rich regions are frequently hypermethylated in cancer tissues, but not methylated in normal tissues. However, there are not many methodological literatures of case-control association studies for high-dimensional DNA methylation data, compared with those of microarray gene expression. One key feature of DNA methylation data is a grouped structure among CpG sites from a gene that are possibly highly correlated. In this article, we proposed a penalized logistic regression model for correlated DNA methylation CpG sites within genes from high-dimensional array data. Our regularization procedure is based on a combination of the l(1) penalty and squared l(2) penalty on degree-scaled differences of coefficients of CpG sites within one gene, so it induces both sparsity and smoothness with respect to the correlated regression coefficients. We combined the penalized procedure with a stability selection procedure such that a selection probability of each regression coefficient was provided which helps us make a stable and confident selection of methylation CpG sites that are possibly truly associated with the outcome.ResultsUsing simulation studies we demonstrated that the proposed procedure outperforms existing main-stream regularization methods such as lasso and elastic-net when data is correlated within a group. We also applied our method to identify important CpG sites and corresponding genes for ovarian cancer from over 20 000 CpGs generated from Illumina Infinium HumanMethylation27K Beadchip. Some genes identified are potentially associated with cancers.

| S-EPMC3348559 | biostudies-literature

Efficient penalized generalized linear mixed models for variable selection and genetic risk prediction in high-dimensional data.

Project description:MotivationSparse regularized regression methods are now widely used in genome-wide association studies (GWAS) to address the multiple testing burden that limits discovery of potentially important predictors. Linear mixed models (LMMs) have become an attractive alternative to principal components (PCs) adjustment to account for population structure and relatedness in high-dimensional penalized models. However, their use in binary trait GWAS rely on the invalid assumption that the residual variance does not depend on the estimated regression coefficients. Moreover, LMMs use a single spectral decomposition of the covariance matrix of the responses, which is no longer possible in generalized linear mixed models (GLMMs).ResultsWe introduce a new method called pglmm, a penalized GLMM that allows to simultaneously select genetic markers and estimate their effects, accounting for between-individual correlations and binary nature of the trait. We develop a computationally efficient algorithm based on penalized quasi-likelihood estimation that allows to scale regularized mixed models on high-dimensional binary trait GWAS. We show through simulations that when the dimensionality of the relatedness matrix is high, penalized LMM and logistic regression with PC adjustment fail to select important predictors, and have inferior prediction accuracy compared to pglmm. Further, we demonstrate through the analysis of two polygenic binary traits in a subset of 6731 related individuals from the UK Biobank data with 320K SNPs that our method can achieve higher predictive performance, while also selecting fewer predictors than a sparse regularized logistic lasso with PC adjustment.Availability and implementationOur Julia package PenalizedGLMM.jl is publicly available on github: https://github.com/julstpierre/PenalizedGLMM.Supplementary informationSupplementary data are available at Bioinformatics online.

| S-EPMC9907224 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data