Software and algorithms for elucidating the structure, function, and evolution of extrachromosomal DNA

Project Summary
Somatic copy number amplification (SCNA) of tumor promoting oncogenes, and focal copy number amplifi-
cations specifically, are a major driver of cancer pathogenicity. Recent results have revealed that that focal
oncogene amplification is mediated to a large extent by extrachromosomal DNA (ecDNA) i.e., large (1.3 Mb
on average), highly amplified, oncogene-containing circular molecules that occur in nearly 25% of cancers
across all sub-types, but rarely in normal cells. Unresolved questions regarding the formation, evolution, het-
erogeneity, and pathogenicity of ecDNA are becoming central to uncovering vulnerabilities that can be targeted
for diagnostics and therapy. The proposed project will enhance and disseminate “Software and algorithms
for elucidating the structure, function, and evolution of extrachromosomal DNA.” Specifically, we will (1) de-
velop CAPER (a Community Accessible Pipeline for EcDNA Reconstruction) by leveraging the GenePattern
ecosystem to provide an easy point and click interface to running the CPU, memory and storage heavy soft-
ware; (2) design and implement novel algorithmic improvements to the CAPER work flow, including support
for long-reads and integration of Omics data; and, (3) enable the broad adoption of CAPER through strategic
collaborations, outreach and education.

Grant Number: 5U24CA264379-05
NIH Institute/Center: NIH
Principal Investigator: Vineet Bafna