EcSeg: Semantic Segmentation of Metaphase Images Containing Extrachromosomal DNA

Oncogene amplification is one of the most common drivers of genetic events in cancer, potently promoting tumor development, growth, and progression. The recent discovery that oncogene amplification commonly occurs on extrachromosomal DNA, driving intratumoral genetic heterogeneity and high copy number owing to its non-chromosomal mechanism of inheritance, raises important questions about how the subnuclear location of amplified oncogenes mediates tumor pathogenesis. Next-generation sequencing is powerful but does not provide spatial resolution for amplified oncogenes, and new approaches are needed for accurately quantifying oncogenes located on ecDNA. Here, we introduce ecSeg, an image analysis tool that integrates conventional microscopy with deep neural networks to accurately resolve ecDNA and oncogene amplification at the single cell level. [Display omitted] •We identify extrachromosomal DNA (ecDNA) in metaphase spreads using deep learning•ecSeg integrates DAPI with FISH probes to provide oncogene amplification location•High intra-tumoral heterogeneity of ecDNA drives cancer pathogenesis Genomics; Bioinformatics; Automation in Bioinformatics