DNA Pooling and Statistical Tests for the Detection of Single Nucleotide Polymorphisms
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David M. Ramsey
Abstract
The development of next generation genome sequencers gives the opportunity of learning more about the genetic make-up of human and other populations. One important question involves the location of sites at which variation occurs within a population. Our focus will be on the detection of rare variants. Such variants will often not be present in smaller samples and are hard to distinguish from sequencing errors in larger samples. This is particularly true for pooled samples which are often used as part of a cost saving strategy. The focus of this article is on experiments that involve DNA pooling. We derive experimental designs that optimize the power of statistical tests for detecting single nucleotide polymorphisms (SNPs, sites at which there is variation within a population). We also present a new simple test that calls a SNP, if the maximum number of reads of a prospective variant across lanes exceeds a certain threshold. The value of this threshold is defined according to the number of available lanes, the parameters of the genome sequencer and a specified probability of accepting that there is variation at a site when no variation is present. On the basis of this test, we derive pool sizes which are optimal for the detection of rare variants. This test is compared with a likelihood ratio test, which takes into account the number of reads of a prospective variant from all the lanes. It is shown that the threshold based rule achieves a comparable power to this likelihood ratio test and may well be a useful tool in determining near optimal pool sizes for the detection of rare alleles in practical applications.
©2012 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
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- ExactDAS: An Exact Test Procedure for the Detection of Differential Alternative Splicing in Microarray Experiments
- Incorporating Genomic Annotation into a Hidden Markov Model for DNA Methylation Tiling Array Data
- Variational Bayes Procedure for Effective Classification of Tumor Type with Microarray Gene Expression Data
- Detecting Differential Expression in RNA-sequence Data Using Quasi-likelihood with Shrunken Dispersion Estimates
- Empirical Bayesian Selection of Hypothesis Testing Procedures for Analysis of Sequence Count Expression Data
- Analyzing Genetic Association Studies with an Extended Propensity Score Approach
- Genotype Copy Number Variations using Gaussian Mixture Models: Theory and Algorithms
- Estimators of the local false discovery rate designed for small numbers of tests
- A PAUC-based Estimation Technique for Disease Classification and Biomarker Selection
- Comparison of Targeted Maximum Likelihood and Shrinkage Estimators of Parameters in Gene Networks
- DNA Pooling and Statistical Tests for the Detection of Single Nucleotide Polymorphisms
Articles in the same Issue
- Article
- Large-scale Parentage Inference with SNPs: an Efficient Algorithm for Statistical Confidence of Parent Pair Allocations
- ExactDAS: An Exact Test Procedure for the Detection of Differential Alternative Splicing in Microarray Experiments
- Incorporating Genomic Annotation into a Hidden Markov Model for DNA Methylation Tiling Array Data
- Variational Bayes Procedure for Effective Classification of Tumor Type with Microarray Gene Expression Data
- Detecting Differential Expression in RNA-sequence Data Using Quasi-likelihood with Shrunken Dispersion Estimates
- Empirical Bayesian Selection of Hypothesis Testing Procedures for Analysis of Sequence Count Expression Data
- Analyzing Genetic Association Studies with an Extended Propensity Score Approach
- Genotype Copy Number Variations using Gaussian Mixture Models: Theory and Algorithms
- Estimators of the local false discovery rate designed for small numbers of tests
- A PAUC-based Estimation Technique for Disease Classification and Biomarker Selection
- Comparison of Targeted Maximum Likelihood and Shrinkage Estimators of Parameters in Gene Networks
- DNA Pooling and Statistical Tests for the Detection of Single Nucleotide Polymorphisms
