Fig. 2

Genes with altered expression associated with nearby SSV breakpoint by distance metric method. a Schematic of the method. For each sample, the relative distances of the SSV breakpoint (BP) closest to the start of each gene are tabulated, with a gene X sample relative distance matrix being assembled. Across samples, the association between expression and relative SSV breakpoint distance for each gene (with a maximum distance of 1 Mb) is then assessed. b Numbers of significant genes (FDR < 5%, linear model correcting for sample cancer type), across 2334 cases with WGS and expression data, for each of the indicated analyses: (1) gene-level CNA versus expression, (2) CNA versus relative distance to closest SSV breakpoint, (3) expression versus SSV breakpoint distance, and (4) expression versus SSV breakpoint distance with correction for gene-level CNA. c Significantly enriched Gene Ontology (GO) terms for genes correlated (FDR < 5% by distance metric method, with corrections for cancer type and CNA) with occurrence of SSV breakpoint in proximity to the gene (for any region considered). p values by one-sided Fisher’s exact test. d Significance of genes in the present study by distance metric method, as plotted (Y-axis) versus significance by genomic region windows method (left, from Fig. 1d, based on 2334 cases, best FDR from the following regions: 0–20 kb upstream, 20–50 kb upstream, 50–100 kb upstream, 0–20 kb downstream, 20–50 kb downstream, 50–100 kb downstream, or within the gene body), and versus the percent of cases impacted (expression > 0.4SD from sample median) by nearby SSV breakpoint (within 1 Mb) without associated amplification or deletion event (defined as log2 tumor/normal copy ratio > 1 or < 1, respectively). Cancer-related, according to refs [14,15,16]. e As examples of significant genes, gene expression levels of BCAR4 (left) and of IGF2 (right), corresponding to SSVs located in the genomic region 1 Mb downstream to 1 Mb upstream of the gene. Each point represents a single case (closest SSV breakpoint represented for each case). Cases with gene amplification are indicated. See also Additional file 1: Figures S2 and S3 and Additional file 5