ArticleNature communications2021
Replicate sequencing libraries are important for quantification of allelic imbalance.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Monoallelic expression characterizes a distinct molecular and clinical group of breast tumors.Research square · 2026Article
- Designing RNA sequencing experiments: A practical guide to reproducible gene expression analysis.Computational and structural biotechnology journal · 2026Review
- Influence of Gonadal and Chromosomal Sex on the Brain Transcriptome in a Mouse Species with Natural Sex Reversal.Molecular biology and evolution · 2025Article
- mNSF: multi-sample non-negative spatial factorization.Genome biology · 2025Article
- Genetic regulation of nascent RNA maturation revealed by direct RNA nanopore sequencing.Genome research · 2025Article
- Article
- Mechanisms of transcriptional regulation inProceedings. Biological sciences · 2024Article
- Genetic regulation of nascent RNA maturation revealed by direct RNA nanopore sequencing.bioRxiv : the preprint server for biology · 2024Article
- Genetic variation is a key determinant of chromatin accessibility and drives differences in the regulatory landscape of C57BL/6J and 129S1/SvImJ mice.Nucleic acids research · 2024Article
- Mechanisms of transcriptional regulation inbioRxiv : the preprint server for biology · 2023Article
- Comparative RNA-sequencing analysis of the prostate in a mouse model of benign prostatic hyperplasia with bladder outlet obstruction.Molecular and cellular biochemistry · 2023Article
- GALNT2, an O-glycosylating enzyme, is a critical regulator of radioresistance of non-small cell lung cancer: evidence from an integrated multi-omics analysis.Cell biology and toxicology · 2023Article
- Foreign RNA spike-ins enable accurate allele-specific expression analysis at scale.Bioinformatics (Oxford, England) · 2023Article
- Foreign RNA spike-ins enable accurate allele-specific expression analysis at scale.bioRxiv : the preprint server for biology · 2023Article
- RNA sequencing-based screen for reactivation of silenced alleles of autosomal genes.G3 (Bethesda, Md.) · 2022Article
- Article
- Uncovering Divergence in Gene Expression Regulation in the Adaptation of Yeast to Nitrogen Scarcity.mSystems · 2021Article
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Authors and funding
6 authors.
Funding
Abstract
A sensitive approach to quantitative analysis of transcriptional regulation in diploid organisms is analysis of allelic imbalance (AI) in RNA sequencing (RNA-seq) data. A near-universal practice in such studies is to prepare and sequence only one library per RNA sample. We present theoretical and experimental evidence that data from a single RNA-seq library is insufficient for reliable quantification of the contribution of technical noise to the observed AI signal; consequently, reliance on one-replicate experimental design can lead to unaccounted-for variation in error rates in allele-specific analysis. We develop a computational approach, Qllelic, that accurately accounts for technical noise by making use of replicate RNA-seq libraries. Testing on new and existing datasets shows that application of Qllelic greatly decreases false positive rate in allele-specific analysis while conserving appropriate signal, and thus greatly improves reproducibility of AI estimates. We explore sources of technical overdispersion in observed AI signal and conclude by discussing design of RNA-seq studies addressing two biologically important questions: quantification of transcriptome-wide AI in one sample, and differential analysis of allele-specific expression between samples.
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