Figure 3: Amplification bias of homologous chromosomes.
From: Calibrating genomic and allelic coverage bias in single-cell sequencing
(a) Schematic illustration of the ‘mixed template model’ and the ‘segregated template model’ reflecting different allele-level contributions to the same locus-level coverage. (Methods, Supplementary Fig. 10). (b) Comparison of the allele coverage predictions (‘Pre.’) from 1 × sequencing depth with the observed coverage at heterozygous sites (‘Obs.’) at 9 × sequencing depth in three single glioblastoma libraries. The combined coverage of reference and alternate bases (red dots) at 9 × sequencing validates the prediction from 1 × sequencing (dashed curve). The allele coverage (reference or alternate) is then predicted from the combined coverage assuming mixed templates (MTM, blue dotted lines) or segregated templates (STM, green dotted lines) and compared with the coverage of reference (blue triangles) or alternate (green triangles) bases at heterozygous sites. The predictions were made from the sequence coverage in disomic Chr. 12 but the agreement with observations in different disomic chromosomes demonstrate that amplification bias is consistent in all chromosomes.
