Figure 1: Genome-wide identification of enhancer-associated insertions.

(a) A subset of variants in tumour genomes occurs within and impacts transcriptional enhancers. ChIP-Seq experiments enrich for enhancer DNA, which may contain either reference sequences or homozygous or heterozygous variants, including insertions. Histone modifications of chromatin surround the DNA where a small insertion (red) creates a transcription factor-binding event, and this sequence is detected in the reads created in the ChIP-Seq experiment. A commonly used sequence alignment algorithm attempts to map reads to the reference genome but discards reads with insertions. Mining these initially discarded reads uncovers enhancer-associated insertions. (b) Genome-wide distribution of sizes of insertions predicted by our ChIP-Seq computational pipeline in 102 samples. The majority of insertions are 1 bp. (c) Left: Histogram showing number of samples in which an insertion is predicted. Insertions predicted in more than two samples (same location, same sequence) are considered separately because they may represent germline polymorphisms in the reference genome. Right: Pie chart depicting proportion of predicted enhancer-associated insertions present in dbSNP, predicted in many samples, or both, suggesting that these variants are acquired in the germline. (d) Counts of enhancer-associated insertions predicted by the pipeline processing each H3K27ac sample. Samples are grouped according to tumour type: GBM, Glioblastoma Multiforme; NB, Neuroblastoma; PaCa, Pancreatic cancer; T-ALL, T cell acute lymphoblastic leukaemia.