G4Beacon: An In Vivo G4 Prediction Method Using Chromatin and Sequence Information

G-quadruplex (G4) structures are critical epigenetic regulatory elements, which usually form in guanine-rich regions in DNA. However, predicting the formation of G4 structures within living cells remains a challenge. Here, we present an ultra-robust machine learning method, G4Beacon, which utilizes the Gradient-Boosting Decision Tree (GBDT) algorithm, coupled with the ATAC-seq data and the surrounding sequences of in vitro G4s, to accurately predict the formation ability of these in vitro G4s in different cell types. As a result, our model achieved excellent performance even when the test set was extremely skewed. Besides this, G4Beacon can also identify the in vivo G4s of other cell lines precisely with the model built on a special cell line, regardless of the experimental techniques or platforms. Altogether, G4Beacon is an accurate, reliable, and easy-to-use method for the prediction of in vivo G4s of various cell lines.