scphaser: haplotype inference using single-cell RNA-seq data

• Published in: Bioinformatics (Oxford, England) Vol. 32; no. 19; pp. 3038 - 3040
• Main Authors: Edsgärd, Daniel, Reinius, Björn, Sandberg, Rickard
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.10.2016
• Subjects: Alleles; Animals; Applications Notes; Genetic Variation; Haplotypes; Humans; Medicin och hälsovetenskap; Mice; RNA; Single-Cell Analysis
• ISSN: 1367-4803; 1367-4811; 1367-4811
• DOI: 10.1093/bioinformatics/btw484

Determination of haplotypes is important for modelling the phenotypic consequences of genetic variation in diploid organisms, including cis-regulatory control and compound heterozygosity. We realized that single-cell RNA-seq (scRNA-seq) data are well suited for phasing genetic variants, since both transcriptional bursts and technical bottlenecks cause pronounced allelic fluctuations in individual single cells. Here we present scphaser, an R package that phases alleles at heterozygous variants to reconstruct haplotypes within transcribed regions of the genome using scRNA-seq data. The devised method efficiently and accurately reconstructed the known haplotype for ≥93% of phasable genes in both human and mouse. It also enables phasing of rare and de novo variants and variants far apart within genes, which is hard to attain with population-based computational inference. scphaser is implemented as an R package. Tutorial and code are available at https://github.com/edsgard/scphaser rickard.sandberg@ki.se Supplementary data are available at Bioinformatics online.