WAWABILITY July 11–12, 2025 Washington DC. Big ideas. Bold Progress. Global Impact. Powered by TDIforAccess.
WAWABILITY July 11–12, 2025 Washington DC. Big ideas. Bold Progress. Global Impact. Powered by TDIforAccess.

A-G.15: Genome wide eccDNA hotspot propensity estimation from confounder aware features

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Studying extrachromosomal circular DNA (eccDNA and ecDNA) can reveal genome instability and regulatory change, especially in cancer disease. Interpreting genome wide recurrence is difficult because apparent hotspots can be inflated by technical and genomic confounders, including low mappability, repeats, and segmental duplications. We therefore move from classifying individual circles to a locus propensity view and learn to rank genomic windows using interpretable context features, while using technical tracks only for filtering and diagnostics. We score recurrence across public experiments from CircleBase v2 in fixed 25 kb bins. For each bin we compute replicate support, defined as the number of independent experiments (unique PubMed ID and assay) that report at least one overlapping eccDNA interval. To define a fair baseline, we keep the number and sizes of eccDNA intervals from each experiment fixed, but randomly shuffle their genomic positions within the same chromosome many times. We then measure how often each bin would be supported under these randomized placements and use the average as the expected background support. Comparing observed support to this baseline provides a measure of the continuous enrichment score used for regression and genome wide ranking tasks. The proposed approach was evaluated along two axes: (i) recovery and tail prioritization of the continuous enrichment signal (random-split = 0.711 ± 0.004, Lift@1% 38, chromosome holdout 0.51, with telomere/centromere ablations probing positional reliance) and (ii) matched comparison to sequence-only methods via the DeepCircle 1 kb balanced classification protocol, where we obtain competitive performance. Co-authors: Delfina Malandrino, Daniele Salerno, Alessia Ture, Rocco Zaccagnino

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