RPASE: Individual‐based allele‐specific expression detection without prior knowledge of haplotype phase

Abstract

Variation in gene expression is believed to make a significant contribution to phenotypic diversity and divergence. The analysis of allele-specific expression (ASE) can reveal important insights into gene expression regulation. We developed a novel method called RPASE (Read-backed Phasing-based ASE detection) to test for genes that show ASE. With mapped RNA-seq data from a single individual and a list of SNPs from the same individual as the only input, RPASE is capable of aggregating information across multiple dependent SNPs and producing individual-based gene-level tests for ASE. RPASE performs well in simulations and comparisons. We applied RPASE to multiple bird species and found a potentially rich landscape of ASE.

Tissue-specific patterns of regulatory changes underlying gene expression differences among Ficedula flycatchers and their naturally occurring F1 hybrids

“…Instead, we used a protocol suitable for natural populations, where polymorphism is abundant, that tests for an association between differential gene expression and allele-specific expression in F 1 hybrids as well as ASE in their parental species. ASE was determined using a novel approach that aggregates information across multiple SNPs in a gene and produces individual-based, gene-level tests for ASE (Wang et al 2018). Segregating variation in cis-regulatory elements forms the basis for ASE in parental species but can also contribute to ASE in F 1 hybrids.…”

“…Additionally, for each sample allelic counts from SNPs that showed evidence of strong mapping bias were removed following Degner et al (2009). We used RPASE to conduct individual-based ASE analyses (Wang et al 2018). To be included in the ASE analysis, we required each gene to contain at least two phased SNPs and each SNP to have minimum coverage of 10 and minimum allelic depth greater than 2.…”

“…By retrieving transcriptomic data across multiple tissues from naturally occurring F 1 hybrids and their parental species, we studied hybrid gene expression in a setting relevant to speciation. We further used a novel statistical approach for detection of ASE particularly developed for natural populations (Wang et al 2018) and also studied signatures of differentiation in candidate cis-regulatory elements. With the help of these complementary approaches, we investigated the role of regulatory changes underlying the evolution of gene expression and Dobzhansky-Muller hybrid incompatibilities between divergent regulatory elements.…”

Direct Chromosomal Phasing: An Easy and Fast Approach for Broadening Prenatal Diagnostic Applicability

“…Phase information is important for a variety of molecular biology scenarios, including allele-specific expression [3,4], compound heterozygosity [5], and prenatal diagnosis [6,7]. In allele-specific expression studies, the altered rate of expression of heterozygous cis-acting variants compared to the normal allele affects gene function and in turn protein expression; therefore, knowledge of the haplotypic arrangements of variants on each homologue would be of significant value [8].…”