Fig. 2: AR ecDNA.
a,b, Gene expression versus genomic alterations (CN gain, red; loss, blue). Promoter methylation for AR (a) and SChLAP1 (b). c, RCFS, that is, average contact frequency within a sliding window applied to the Hi-C contact matrix for each sample (row) showing a depletion of local contacts (low RCFS) surrounding the AR locus in a subset of samples, which were enriched for samples with ecDNA events detected by WGS at this region. The local TAD structure (black points indicating the TAD edges) is annotated. Right, the corresponding sample meta-data includes the average RCFS between AR enhancer and transcription start site (TSS), CN, AR TPM, A and B domain call, and the degree of cyclical amplification (indicating ecDNA) from AmpliconArchitect. Tiles with a gray fill represent values not available. d, Bin pair contact frequencies surrounding the AR locus for a single ecDNA+ sample above the diagonal and a single ecDNA− sample below the diagonal, further illustrating the contrast in contact frequency. The region circled in white shows an increased interaction between the two ends of the ecDNA region, which is consistent with circularization. e, Per-sample AR TPM versus RCFS; the red dashed line is the same cutoff for categorizing samples as depleted versus typical AR RCFS as in c. f,g, Kaplan–Meier curves showing OS as a function of RCFS (high in f, low in g) and whether an ASI was used as the next-line therapy after biopsy (solid line, true; dotted line, false; interaction P = 0.0051). HR, Cox hazard ratio. ANOVA, analysis of variance.
