QuadStack: Specialized convolutional blocks enable in vivo BG4-binding motif prediction and highlight discrepancies with in vitro G-quadruplexes. (opens in new tab)

G-quadruplex (G4) prediction has been largely guided by in vitro biophysical rules, yet these models show limited agreement with in vivo measurements. Here, we present QuadStack, a deep learning model trained on a multi study BG4-ChIP-seq compendium. QuadStack introduces two biologically grounded convolutional modules-G4Stack Convolution, which captures G/C stacking patterns, and Reverse Complement Convolution, which enforces strand invariant representations consistent with ChIP-seq signals. ...