Dataset Information

M(3)-S: a genotype calling method incorporating information from samples with known genotypes.

ABSTRACT: A key challenge in analyzing high throughput Single Nucleotide Polymorphism (SNP) arrays is the accurate inference of genotypes for SNPs with low minor allele frequencies. A number of calling algorithms have been developed to infer genotypes for common SNPs, but they are limited in their performance in calling rare SNPs. The existing algorithms can be broadly classified into three categories, including: population-based methods, SNP-based methods, and a hybrid of the two approaches. Despite the relatively better performance of the hybrid approach, it is still challenging to analyze rare SNPs.We propose to utilize information from samples with known genotypes to develop a two stage genotyping procedure, namely M(3)-S, for rare SNP calling. This new approach can improve genotyping accuracy through clearly defining the boundaries of genotype clusters from samples with known genotypes, and enlarge the call rate by combining the simulated data based on the inferred genotype clusters information with the study population.Applications to real data demonstrates that this new approach M(3)-S outperforms existing methods in calling rare SNPs.

SUBMITTER: Li G

PROVIDER: S-EPMC4669649 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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M(3)-S: a genotype calling method incorporating information from samples with known genotypes.

Li Gengxin G Zhao Hongyu H

BMC bioinformatics 20151203

<h4>Background</h4>A key challenge in analyzing high throughput Single Nucleotide Polymorphism (SNP) arrays is the accurate inference of genotypes for SNPs with low minor allele frequencies. A number of calling algorithms have been developed to infer genotypes for common SNPs, but they are limited in their performance in calling rare SNPs. The existing algorithms can be broadly classified into three categories, including: population-based methods, SNP-based methods, and a hybrid of the two appro ...[more]

PMID: 26634345

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Project description:BackgroundAmong the primary goals of microarray analysis is the identification of genes that could distinguish between different phenotypes (feature selection). Previous studies indicate that incorporating prior information of the genes' function could help identify physiologically relevant features. However, current methods that incorporate prior functional information do not provide a relative estimate of the effect of different genes on the biological processes of interest.ResultsHere, we present a method that integrates gene ontology (GO) information and expression data using Bayesian regression mixture models to perform unsupervised clustering of the samples and identify physiologically relevant discriminating features. As a model application, the method was applied to identify the genes that play a role in the cytotoxic responses of human hepatoblastoma cell line (HepG2) to saturated fatty acid (SFA) and tumor necrosis factor (TNF)-alpha, as compared to the non-toxic response to the unsaturated FFAs (UFA) and TNF-alpha. Incorporation of prior knowledge led to a better discrimination of the toxic phenotypes from the others. The model identified roles of lysosomal ATPases and adenylate cyclase (AC9) in the toxicity of palmitate. To validate the role of AC in palmitate-treated cells, we measured the intracellular levels of cyclic AMP (cAMP). The cAMP levels were found to be significantly reduced by palmitate treatment and not by the other FFAs, in accordance with the model selection of AC9.ConclusionsA framework is presented that incorporates prior ontology information, which helped to (a) perform unsupervised clustering of the phenotypes, and (b) identify the genes relevant to each cluster of phenotypes. We demonstrate the proposed framework by applying it to identify physiologically-relevant feature genes that conferred differential toxicity to saturated vs. unsaturated FFAs. The framework can be applied to other problems to efficiently integrate ontology information and expression data in order to identify feature genes.

Dataset Information

M(3)-S: a genotype calling method incorporating information from samples with known genotypes.

Publications

M(3)-S: a genotype calling method incorporating information from samples with known genotypes.

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