Dataset Information

Variant association tools for quality control and analysis of large-scale sequence and genotyping array data.

ABSTRACT: Currently there is great interest in detecting associations between complex traits and rare variants. In this report, we describe Variant Association Tools (VAT) and the VAT pipeline, which implements best practices for rare-variant association studies. Highlights of VAT include variant-site and call-level quality control (QC), summary statistics, phenotype- and genotype-based sample selection, variant annotation, selection of variants for association analysis, and a collection of rare-variant association methods for analyzing qualitative and quantitative traits. The association testing framework for VAT is regression based, which readily allows for flexible construction of association models with multiple covariates and weighting themes based on allele frequencies or predicted functionality. Additionally, pathway analyses, conditional analyses, and analyses of gene-gene and gene-environment interactions can be performed. VAT is capable of rapidly scanning through data by using multi-process computation, adaptive permutation, and simultaneously conducting association analysis via multiple methods. Results are available in text or graphic file formats and additionally can be output to relational databases for further annotation and filtering. An interface to R language also facilitates user implementation of novel association methods. The VAT's data QC and association-analysis pipeline can be applied to sequence, imputed, and genotyping array, e.g., "exome chip," data, providing a reliable and reproducible computational environment in which to analyze small- to large-scale studies with data from the latest genotyping and sequencing technologies. Application of the VAT pipeline is demonstrated through analysis of data from the 1000 Genomes project.

SUBMITTER: Wang GT

PROVIDER: S-EPMC4067555 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Variant association tools for quality control and analysis of large-scale sequence and genotyping array data.

Wang Gao T GT Peng Bo B Leal Suzanne M SM

American journal of human genetics 20140501 5

Currently there is great interest in detecting associations between complex traits and rare variants. In this report, we describe Variant Association Tools (VAT) and the VAT pipeline, which implements best practices for rare-variant association studies. Highlights of VAT include variant-site and call-level quality control (QC), summary statistics, phenotype- and genotype-based sample selection, variant annotation, selection of variants for association analysis, and a collection of rare-variant a ...[more]

PMID: 24791902

Similar Datasets

Project description:ChIP-seq has become the primary method for identifying in vivo protein-DNA interactions on a genome-wide scale, with nearly 800 publications involving the technique appearing in PubMed as of December 2012. Individually and in aggregate, these data are an important and information-rich resource. However, uncertainties about data quality confound their use by the wider research community. Recently, the Encyclopedia of DNA Elements (ENCODE) project developed and applied metrics to objectively measure ChIP-seq data quality. The ENCODE quality analysis was useful for flagging datasets for closer inspection, eliminating or replacing poor data, and for driving changes in experimental pipelines. There had been no similarly systematic quality analysis of the large and disparate body of published ChIP-seq profiles. Here, we report a uniform analysis of vertebrate transcription factor ChIP-seq datasets in the Gene Expression Omnibus (GEO) repository as of April 1, 2012. The majority (55%) of datasets scored as being highly successful, but a substantial minority (20%) were of apparently poor quality, and another ?25% were of intermediate quality. We discuss how different uses of ChIP-seq data are affected by specific aspects of data quality, and we highlight exceptional instances for which the metric values should not be taken at face value. Unexpectedly, we discovered that a significant subset of control datasets (i.e., no immunoprecipitation and mock immunoprecipitation samples) display an enrichment structure similar to successful ChIP-seq data. This can, in turn, affect peak calling and data interpretation. Published datasets identified here as high-quality comprise a large group that users can draw on for large-scale integrated analysis. In the future, ChIP-seq quality assessment similar to that used here could guide experimentalists at early stages in a study, provide useful input in the publication process, and be used to stratify ChIP-seq data for different community-wide uses.

Dataset Information

Variant association tools for quality control and analysis of large-scale sequence and genotyping array data.

Publications

Variant association tools for quality control and analysis of large-scale sequence and genotyping array data.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets