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Volume 74, Issue 5, Pages (November 2018)

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1 Volume 74, Issue 5, Pages 551-559 (November 2018)
Spatial Intratumor Genomic Heterogeneity within Localized Prostate Cancer Revealed by Single-nucleus Sequencing  Fei Su, Wei Zhang, Dalei Zhang, Yaqun Zhang, Cheng Pang, Yingying Huang, Miao Wang, Luwei Cui, Lei He, Jinsong Zhang, Lihui Zou, Junhua Zhang, Wenqinq Li, Lin Li, Jianyong Shao, Jie Ma, Fei Xiao, Ming Liu  European Urology  Volume 74, Issue 5, Pages (November 2018) DOI: /j.eururo Copyright © Terms and Conditions

2 Fig. 1 (A) Overview of the study design. (B) Lorenz curve of coverage uniformity for all samples sequenced in this study, including 17 single tumor cells, three normal cells, and one blood sample. (C) Comparison of the mutational density of all samples G3 (n=13), G4 (n=4), Ren (2017) (n=65), TCGA-PRAD (n=499), and ICGC (n=200). In each box plot, the lower and upper limits of the box denote the 25th (Q1) and 75th (Q3) percentiles, and the median value is indicated. The upper and lower whiskers show Q3+1.5×IQR and Q1 − 1.5×IQR, respectively. (D) The percentage of mutational signatures in each sample, which was identified by deconstructSigs. IQR=interquartile range. European Urology  , DOI: ( /j.eururo ) Copyright © Terms and Conditions

3 Fig. 2 Integrative landscape analysis of somatic aberrations in prostate obtained through single-cell genome sequencing. Top, the number of silent/non-silent mutations and Gleason scores of each sample. Middle, top 80 most often mutated genes in our cohort. The different blocks in heat map from right to left are samples from P1, P2, and control samples. Right, gene catalogues are indicated in different colors. Samples are displayed as columns. European Urology  , DOI: ( /j.eururo ) Copyright © Terms and Conditions

4 Fig. 3 Copy number alterations (CNAs) in our cohort. (A) Fraction of genomic regions affected by CNAs between different Gleason scores. (B) GISTIC2.0 analysis showing mapping of regions of significant chromosomal amplification or deletion throughout the genome in P2. Cytoband labels indicate significant calls (FDR < 0.1). (C) Heatmap showing the copy number states evaluated by single-cell whole genome sequencing data in P2. Horizontal axis corresponds to the position of genome. Copy number of windows of 5 Kb in size are indicated. European Urology  , DOI: ( /j.eururo ) Copyright © Terms and Conditions

5 Fig. 4 Complex structural rearrangements in prostate cancer. Circos plot depicts the related genes (TSG: red; Oncogene: blue; Kinase: violet) in the outer ring and genomic location in the inner ring. Interchromosomal translocations and intrachromosomal rearrangements are shown in red and blue, respectively. Genomes are organized according to the number of genes. European Urology  , DOI: ( /j.eururo ) Copyright © Terms and Conditions

6 Fig. 5 (A) and (B) Phylogenetic results inferred by OncoNEM on single-cell prostate cancer dataset. Edge lengths stand for branch length for the tree. Green node indicates the normal cells, blue indicates the unobserved nodes, red indicates the tumor cells with Gleason score 4, orange indicates the tumor cells with Gleason score 3, and purple indicates the mixed node. (C) Box plots depicting the heterogeneity index (HI). All pairwise samples were divided into three groups: G3-G3, G3-G4, and G4-G4. (D) Spearman correlation coefficients are calculated based on the HI in each sample. Values of coefficient from low to high are colored from red to blue. European Urology  , DOI: ( /j.eururo ) Copyright © Terms and Conditions


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