• Media type: E-Article
  • Title: Towards in silico CLIP-seq: predicting protein-RNA interaction via sequence-to-signal learning
  • Contributor: Horlacher, Marc; Wagner, Nils; Moyon, Lambert; Kuret, Klara; Goedert, Nicolas; Salvatore, Marco; Ule, Jernej; Gagneur, Julien; Winther, Ole; Marsico, Annalisa
  • imprint: Springer Science and Business Media LLC, 2023
  • Published in: Genome Biology
  • Language: English
  • DOI: 10.1186/s13059-023-03015-7
  • ISSN: 1474-760X
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>We present RBPNet, a novel deep learning method, which predicts CLIP-seq crosslink count distribution from RNA sequence at single-nucleotide resolution. By training on up to a million regions, RBPNet achieves high generalization on eCLIP, iCLIP and miCLIP assays, outperforming state-of-the-art classifiers. RBPNet performs bias correction by modeling the raw signal as a mixture of the protein-specific and background signal. Through model interrogation via Integrated Gradients, RBPNet identifies predictive sub-sequences that correspond to known and novel binding motifs and enables variant-impact scoring via in silico mutagenesis. Together, RBPNet improves imputation of protein-RNA interactions, as well as mechanistic interpretation of predictions.</jats:p>
  • Access State: Open Access