Modeling allele-specific expression at the gene and SNP levels simultaneously by a Bayesian logistic mixed regression model

• Published in: BMC bioinformatics 2019-10, Vol.20 (1), p.530-13, Article 530
• Main Authors: Xie, Jing, Ji, Tieming, Ferreira, Marco A R, Li, Yahan, Patel, Bhaumik N, Rivera, Rocio M
• Format: Article
• Language: English
• Subjects: Algorithms; Alleles; Allelic imbalance; Analysis; Animal genetics; Animals; Bayes Theorem; Biochemistry; Cattle; Chromosomes; Gene Expression; Genes; Genetic polymorphisms; Genomes; Genomics; Hierarchical generalized linear mixed model; High-Throughput Nucleotide Sequencing - methods; High-throughput sequencing experiments; Humans; Logistic Models; Methodology; Models, Genetic; Polymorphism, Single Nucleotide; Power (Philosophy); Reproducibility of Results; Single nucleotide polymorphism; Single nucleotide polymorphisms; Statistical methods
• ISSN: 1471-2105; 1471-2105
• DOI: 10.1186/s12859-019-3141-6

High-throughput sequencing experiments, which can determine allele origins, have been used to assess genome-wide allele-specific expression. Despite the amount of data generated from high-throughput experiments, statistical methods are often too simplistic to understand the complexity of gene expression. Specifically, existing methods do not test allele-specific expression (ASE) of a gene as a whole and variation in ASE within a gene across exons separately and simultaneously. We propose a generalized linear mixed model to close these gaps, incorporating variations due to genes, single nucleotide polymorphisms (SNPs), and biological replicates. To improve reliability of statistical inferences, we assign priors on each effect in the model so that information is shared across genes in the entire genome. We utilize Bayesian model selection to test the hypothesis of ASE for each gene and variations across SNPs within a gene. We apply our method to four tissue types in a bovine study to de novo detect ASE genes in the bovine genome, and uncover intriguing predictions of regulatory ASEs across gene exons and across tissue types. We compared our method to competing approaches through simulation studies that mimicked the real datasets. The R package, BLMRM, that implements our proposed algorithm, is publicly available for download at https://github.com/JingXieMIZZOU/BLMRM . We will show that the proposed method exhibits improved control of the false discovery rate and improved power over existing methods when SNP variation and biological variation are present. Besides, our method also maintains low computational requirements that allows for whole genome analysis.