Fig. 1: The Genetic landscape of AML based on single-cell DNA sequencing.

a Distribution of the number of total sequenced cells. Each point represents a sample from unique patients. b Somatic mutations in 735,483 cells from 123 AML patients detected by single-cell DNA sequencing (scDNA-seq). Each column represents a cell at the indicated scale, and cells from the same case are clustered together within the areas surrounded by the gray lines. Cells that were genotyped as being mutated or wild type for the indicated gene are colored in blue and white, respectively. Cells with missing genotypes are colored in gray. When one sample has multiple different mutations in the same gene, they were annotated differently (e.g., DNMT3A_a and DNMT3A_b). Mutated genes are colored based on the affected molecular pathway (nucleophosmin colored in green, DNA methylation in orange, RTK/RAS/MAP kinase pathway in blue, JAK-STAT pathway in brown, transcription factor in red, chromatin/cohesin in light green, splicing in pink, and apoptosis in purple). A total of 76,549 cells that were genotyped as wild type for all the variants screened are not shown. c Correlation of the variant allele fraction (VAF) from bulk-sequencing and scDNA-seq. The x-axis shows the VAF from scDNA-seq (scDNA-seq VAF). The y-axis shows the VAF from the bulk sequencing (bulk VAF). Each dot represents a detected variant. The line represents a linear regression line. The shaded area represents the 95% confidence intervals. d A representative case with highly homozygous variant involving copy-neutral loss of heterozygosity (CN-LOH). Heat map (left) shows the genotype of each sequenced cell for each variant, with clustering based on the genotypes of driver mutations. Each column represents a cell at the indicated scale. Cells with homozygous mutation, heterozygous mutation, and wild-type cells are indicated in red, blue, and white, respectively. Cells with missing genotypes are indicated in gray. The allele counts distribution is shown to the right. The allele count is shown on the vertical axis, and the chromosomes are shown on the horizontal axis. Chromosome 13 involving highly homozygous FLT3-ITD is highlighted with a blue rectangle. Mut-Homo homozygously mutated, Mut-Hetero heterozygously mutated, WT wild type, Missing missing genotype.