We report a newly-identified bias in CLIP data that results from cleaving enzyme specificity. This bias is inadvertently incorporated into standard peak calling methods, which identify the most likely locations where proteins bind RNA. We further show how, in downstream analysis, this bias is incorporated into models inferred by the state-of-the-art GraphProt method to predict protein RNA-binding. We call for both experimental controls to measure enzyme specificities and algorithms to identify unbiased CLIP binding sites.
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