scDNA-seq and LOH monitoring in yeast aging

 single cell DNA seq

Natural communication, 2019, Luquette, .. Peter Park, Identification of somatic mutations in single cell DNA-seq using  a spatial model of allelic imbalance. 

somatic SNV (single nucleotide variation). 

variant allele fraction (VAF), the fraction of sequencing reads supporting allele a heterozygous variant. 

Qin: VAF on loss of heterozygosity during aging can be done with young cells as the background. The young cells provide a reference distribution of VAF at allelic positions genome-wide. Comparison between VAF of aging cells and young cells. If loss of heterozygocity occurs a loci, VAF at a loci can only be caused by amplification artifacts, which are expect to be 'random' and has a very small probability to overlap with the natural variations. S288c and RM is 0.5-1%. 

Luquette19 proposed a genome-location spatial model for Amplification Balance to evaluate VAF.  Luquette used nearby known SNP VAF to show the allele imbalance.  Luquette19 used a 'smooth curve' to model the spatial distribution of allele imbalance on chromosomes.