PMC

(A) Algorithm workflow for a given target region. (B) Illustration of reads with ‘misaligned’ sequences that are soft-clipped by the alignment tool or paired-end reads with unmapped mates are extracted to use for building contigs. The locations of the discordantly mapped paired-end reads with signatures suggestive of inversions, tandem duplications and translocations are stored and used for downstream analysis and filtering. (C) BreaKmer assembly process using the kmer subtraction procedure to iteratively build contigs.

(A) A circos plot displaying links between gene partners and their genomic locations for the known translocations. (B) BreaKmer analysis results for the 38 cancer specimens and 80 ‘normal’ controls. For the 18 known SV events listed in the table rows, the true-positive (gray rectangle) and false-negative (red rectangle) results are shown for each replicate analyzed with the corresponding SV. The rectangles in the center are spaced to indicate separate samples. Boxplots on the right show the distributions of total read support (black boxplots) with the read depth (gray boxplots) at the inferred breakpoints for each of the known variants detected by BreaKmer. (C) A circos plot showing the validated novel translocation partners and their genomic locations identified by BreaKmer.

Plots displaying the relations between sequence read evidence and read depths. (A) A scatterplot showing the relation between the total read support (RS) for the known SV events identified from the BreaKmer analysis and the maximum sequence read depth (RD) observed at the inferred SV breakpoints on the log scale. Each point represents a replicate in which a true-positive call was made by BreaKmer, and the point color corresponds to the known SV of the sample replicate. (B) A scatterplot showing the relation between the quantity of the two types of sequence read evidence identified by BreaKmer for translocations. Each point represents a replicate with a known translocation that BreaKmer properly identified with the log transformed number of assembled reads (AS) on the x-axis and the log transformed number of discordantly mapped read pairs (DR) on the y-axis. (C) Boxplots showing the distributions of the BreaKmer inferred breakpoint read depth (RD, top panel) in relation to the amount of total read support (RS, bottom panel) of the identified known translocations for the four samples with tumor purity dilution replicates.