Amplicon Architect (AA) is a tool that can reconstruct focally amplified genomic regions in cancer samples using whole genome sequencing. Utilizing dynamic programming, it identifies breakpoints in these regions and non-overlapping intervals, known as amplicons, to reveal the original structure and provide essential biological insight into the user's cancer samples. There are amplicon classifications that the tool categorizes each amplicon into: extrachromosomal DNA (ecDNA), Breakage fusion bridge (BFB), Linear amplification, or complex non-cyclic. The problem with the tool is that although it contains a lot of illuminating output, it is quite difficult to interpret for users, especially those without a computational background.
Where has AA been used?
Amplicon Architect was recently employed in a study to reconstruct focal genomic alterations for the malignancies neuroblastoma and glioma. In studies of more than sixty cancer patients with viral contamination in this study, a startling quantity of amplification of DNA with distinct physical properties, indicative of both human-virus extrachromosomal DNA, was discovered. Numerous pan-cancer datasets' investigations of reassembled amplicons have revealed the crucial role that ecDNA plays in the emergence of localized exaggerations and diverse readjustments in the cancer subtype spectrum.
ecDNA: when a small DNA fragment separates from chromosome and becomes circular
BFB: when the chromosome undergoes telomere loss, fusion with another chromosome, and mitotic spindle stress that results in genomic instability
Linear: Small segment of DNA duplicates linearly, creating multiple copies of the segment
Complex Non-cyclic: Segment of DNA is duplicated in a non-linear fashion, resulting in a complex rearrangement
Leader: Rohil