On the limits of inferring biophysical parameters of RBP-RNA interactions from in vitro RNA Bind’n Seq data

TL;DR

This paper explores the limitations of using RNA Bind’n Seq data to infer how RNA binding proteins interact with RNA in a lab setting.

Contribution

The paper introduces a thermodynamic model and uses expectation-maximization to infer RBP binding specificities from RNA Bind’n Seq data.

Findings

The model successfully reproduces known RBP specificities and predicts novel, longer binding motifs.

The model fails to recover all known motifs, suggesting RNA Bind’n Seq data may not fully align with a single biophysical model.

Abstract

We develop a thermodynamic model describing the binding of RNA binding proteins (RBP) to oligomers in vitro. We apply expectation-maximization to infer the specificity of RBPs, represented as position-specific weight matrices (PWMs), by maximizing the likelihood of RNA Bind’n Seq data from the ENCODE project. We demonstrate that the model can reproduce known specificities for well-studied proteins and that in some cases we predict novel, longer binding motifs. However, the model does not recover all the motifs that are in principle known, indicating that the data is not well explained by a single underlying biophysical model. Our code is publicly available.

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