Identifying HSRs

[prashanthid]

Hi authors,

Thank you for your wonderful tool. I applied AmpliconArchitect for identification and AmpliconClassifier for classification of ecDNAs in resistance and vehicle models. I obtained large heavily rearranged amplicons in one resistance model while ecDNA in another resistance model. Is there a way to identify HSR events bioinformatically from AmpliconArchitect/AmpliconClassifier results? Or any clues to infer HSR events from SV cycle plot?

Thank you,
Prashanthi

[jluebeck]

Hi Prashanthi,

One thing you might consider looking for (using AA outputs or other SV detection tools), are breakpoints linking the focal amplification region to things outside the focally amplified area. These may represent the signatures of HSRs. It's important to note that short reads may have limitations in their ability to reliably detect HSRs, when linking focal amplifications to repetitive or low complexity regions of the genome. We've had luck using long read/optical mapping data to detect HSRs in a more convincing way (including a collaboration with the Thomas Graeber Lab at UCLA).

To give a more targeted answer to your question though - at the moment we do not provide any formal tools for the detection of HSR status using AA/AC alone, however our other tools (AmpliconReconstructor & FaNDOM) can be used for those purposes given optical mapping data.

Happy to discuss more over email if you'd like!
Jens

[prashanthid]

Hi Jens,

Thank you very much for the clarification. I would love to discuss with you further over email.

Regards,
Prashanthi