AmpliconSuite: an end-to-end workflow for analyzing focal amplifications in cancer genomes - imaging datasets

Focal amplifications in the cancer genome, particularly extrachromosomal DNA (ecDNA) are pivotal in cancer progression yet bioinformatically challenging to identify. We present AmpliconSuite, a collection of tools enabling robust identification of focal amplifications from whole-genome sequencing. AmpliconSuite includes AmpliconSuite-pipeline; utilizing the AmpliconArchitect (AA) method, and AmpliconClassifier (AC) for categorizing amplifications. We assembled a collection of 175 metaphase FISH-validated amplifications across 72 models, demonstrating accurate predictions by AC. We also introduce ecContext for classifying ecDNA formation mechanisms. Analysis of 6,506 patient pan-cancer samples revealed ecDNA-mediated oncogene co-amplification patterns, demonstrating ecDNA is responsible for more than 70% of CDK4-MDM2 co-amplifications, and co-opts neighboring oncogenes and frequently co-opts neighboring chromatin remodeling genes. To democratize data sharing, we created AmpliconRepository.org, a community-editable platform for sharing focal amplification calls featuring interactive visualizations, cross-project batch downloads, and a co-amplification analysis tool, enabling systematic investigation of focal amplification biology across >15,000 hosted samples.