Journal: Nucleic Acids Research

Article Title: Genome-wide copy number profiling of single cells in S-phase reveals DNA-replication domains

doi: 10.1093/nar/gks1352

Figure Lengend Snippet: Log2 intensity ratios in S-phase cells oscillate according to predicted replication timing. For each single-cell and multi-cell control sample, a heat map of the mean log2 intensity ratio per replication domain across all autosomes is depicted in a circosplot. The colour-code legend of the heat map is depicted at the bottom of the figure. In each circosplot, the outermost circle depicts the predicted replication timing pattern as published by Ryba et al. (early replicating domains in green; late replicating domains in red; replication domains covered by five or more microarray probes are marked by a blue bar on the outside). This is followed (from the outside to the inside of the circosplot) by the heat maps representing all single-cell log2 intensity ratio data (one cell per rim) and subsequently by the heat maps reflecting all multi-cell control log2 intensity ratio data (one multi-cell control per rim). ( a and b ) All S-phase single-cell and multi-cell samples. The top circosplot depicts the chromosomes 1 to 8 (a), bottom circosplot chromosomes 9 to 22 (b). The 14 S-phase single cell samples are shown in the following order (outside to inside): S1.3, S1.2, S3.1, S7.5, S7.6, S1.4, S7.7, S1.1, S7.1, S7.4, S4.1, S4.2, S7.2 and S7.3; followed by S-phase multi-cell control samples. ( c and d ) All G1- and G2/M-phase single-cell and multi- cell samples. Top circosplot depicts the chromosomes 1 to 8 (c), bottom circosplot chromosomes 9 to 22 (d). The 16 single-cell samples are shown in the following order (outside to inside): G1.1, G1.2, G1.3, G1.4, G3.1, G4.1, G7.1, G7.2, M1.1, M1.2, M1.3, M3.1, M3.2, M4.1, M7.1 and M7.2; followed by G1- and G2/M-phase multi-cell control samples. The oscillating pattern of consecutive positive and negative log2 intensity ratios genome wide orchestrated by early and late DNA replication in S-phase single cells can be clearly observed, and is concordant with the pattern in multi-cell controls. In contrast, the G1-phase and G2/M-phase single cells do not demonstrate such genome wide oscillation of log2 intensity ratios in accordance with the replication timing pattern. Similar observations can be made for the multi-cell controls. Three specific regions for which the log2 intensity plots are shown in Supplementary Figure S5 at high resolution are marked by a black box.

Article Snippet: Scanning was performed using a DNA-microarray scanner (Agilent Technologies) for 24sure slides and a Genepix 4000 B (Axon instruments—Molecular Devices) for Constitutional Chip 4.0 slides.

Techniques: Microarray, Genome Wide