RNAct: Protein-RNA interaction predictions for model organisms with supporting experimental data

Abstract

Protein-RNA interactions are implicated in a number of physiological roles as well as diseases, with molecular mechanisms ranging from defects in RNA splicing, localization and translation to the formation of aggregates. Currently, ∼1400 human proteins have experimental evidence of RNA-binding activity. However, only ∼250 of these proteins currently have experimental data on their target RNAs from various sequencing-based methods such as eCLIP. To bridge this gap, we used an established, computationally expensive protein-RNA interaction prediction method, catRAPID, to populate a large database, RNAct. RNAct allows easy lookup of known and predicted interactions and enables global views of the human, mouse and yeast protein-RNA interactomes, expanding them in a genome-wide manner far beyond experimental data (http://rnact.crg.eu).

Figure 1.

(A) Interaction propensity scores for the background (sampled from slightly over 2 billion human protein–RNA pairs; light red) and positive set (212 256 high-confidence protein–RNA interactions revealed by eCLIP; cyan). The z-score reported in the results pages is computed on the right-skewed blue distribution, with the solid cyan line indicating the mean and the dashed line indicating a z-score of 1 (one standard deviation above the mean). (B) The area under the ROC curve of 0.78 (0.72 upon length normalization) indicates the predictive performance of the catRAPID method on recent high-confidence experimental eCLIP data from the ENCODE project.

Figure 2.

Search results (disambiguation page). This page allows selection of the protein or RNA of interest across the 3 species currently in RNAct.

Figure 3.

The Protein view. This page shows a list of potential RNA interaction partners prioritized by catRAPID length-normalized prediction score. Alternatively, the page can be sorted by eCLIP experimental results by clicking on the ‘P-value’ or ‘fold change’ columns. Useful information on the protein of interest, such as whether it is a known or predicted RBP and whether experimental interaction data (e.g. from eCLIP experiments) exists for it is shown at the top of this view, and transcript annotation and quality information are shown as badges for each RNA. Links out to Ensembl and UniProt are provided. Other links lead to the protein’s or RNA’s view within RNAct.