Horlacher, M. ; Wagner, N.* ; Moyon, L. ; Kuret, K.* ; Goedert, N. ; Salvatore, M.* ; Ule, J.* ; Gagneur, J. ; Winther, O.* ; Marsico, A.
Towards in silico CLIP-seq: predicting protein-RNA interaction via sequence-to-signal learning.
Genome Biol. 24:180 (2023)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Clip-seq ; Computational Biology ; Deep Learning ; Protein-rna Interaction; Binding Protein; Sites; Specificities; Discovery; Specify; Motifs
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Language
english
Publication Year
2023
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0
HGF-reported in Year
2023
ISSN (print) / ISBN
1474-760X
e-ISSN
1465-6906
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Volume: 24,
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Article Number: 180
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Bmc
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Campus, 4 Crinan St, London N1 9xw, England
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Reviewing status
Peer reviewed
POF-Topic(s)
30205 - Bioengineering and Digital Health
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-503800-001
G-503800-004
Grants
Wellcome Trust
Copyright
Erfassungsdatum
2023-10-06