Fig. 4: SDR-seq to profile primary samples from individuals with B cell lymphoma.
From: Functional phenotyping of genomic variants using joint multiomic single-cell DNA–RNA sequencing
a, Outline of the experiment. Primary samples and target panels are indicated. b, Uniform manifold approximation and projection (UMAP) highlighting the different samples clustered by either gene expression (RNA) or variants (gDNA). The numbers of cells for each sample are indicated as a bar graph. c, UMAP highlighting the maturation states clustered by either gene expression (RNA) or variants (gDNA). The numbers of cells within a maturation state are indicated as a bar graph (percentage of total); Mem, memory B cells. d, Variants detected in the experiment. Color indicates the percentage within B cells and non-B cells for each variant. Samples and HET/ALT alleles are indicated by color. Venn diagram showing the overlap of variants that occur with more than 5% frequency in each sample. e, Subset cells for DZ and LZ maturation states clustered by variants (gDNA) with clones indicated by color for each sample. The numbers of cells within DZ or LZ maturation states are indicated as a bar graph (percentage of total). f, Differentially abundant variants between DZ and LZ states (P < 0.05, χ2 test with a Benjamini–Hochberg correction). Summed counts of genes that the variants map to are shown in a bar graph. ΔDZ – LZ (percentage of the respective allele in DZ minus LZ) is shown in a heat map. Genes that the variants map to and patient of origin are indicated by color. g, Gene expression of the most frequently differentially expressed genes across samples in LZ and DZ states. Color indicates expression (z score, data are scaled by column), primary samples and maturation state. h, Gene Ontology (GO) term analysis of the most frequently differentially expressed genes. P values were computed using a Fisher’s exact test with the weight01 algorithm (topGO), correcting for GO hierarchy structure. cell., cellular; comp., compounds; DE, differentially expressed; proc., process; resp., response; trans., transduction. i, Genes involved in B cell receptor signaling in cells with high (top 20%) and low (bottom 20%) variant burden in DZ and LZ states. Color indicates expression (z score, data are scaled by column), primary samples, genes, maturation state and variant burden.
