Integration of CLIP experiments of RNAbinding proteins: a novel approach to predict context-dependent splicing factors from transcriptomic data
Keywords: 
Alternative splicing
Splicing factor
RNA-binding protein
RNA-seq
CLIP-seq
Issue Date: 
2019
Publisher: 
Springer Science and Business Media LLC
ISSN: 
1471-2164
Note: 
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Citation: 
Carazo Melo, F.(Fernando); Gimeno, M. (Marian); Ferrer-Bonsoms, J.A. (Juan A.); et al. "Integration of CLIP experiments of RNAbinding proteins: a novel approach to predict context-dependent splicing factors from transcriptomic data". BMC Genomics. 20 (521), 2019, 1 - 11
Abstract
Background: Splicing is a genetic process that has important implications in several diseases including cancer. Deciphering the complex rules of splicing regulation is crucial to understand and treat splicing-related diseases. Splicing factors and other RNA-binding proteins (RBPs) play a key role in the regulation of splicing. The specific binding sites of an RBP can be measured using CLIP experiments. However, to unveil which RBPs regulate a condition, it is necessary to have a priori hypotheses, as a single CLIP experiment targets a single protein. Results: In this work, we present a novel methodology to predict context-specific splicing factors from transcriptomic data. For this, we systematically collect, integrate and analyze more than 900 CLIP experiments stored in four CLIP databases: POSTAR2, CLIPdb, DoRiNA and StarBase. The analysis of these experiments shows the strong coherence between the binding sites of RBPs of similar families. Augmenting this information with expression changes, we are able to correctly predict the splicing factors that regulate splicing in two gold-standard experiments in which specific splicing factors are knocked-down. Conclusions: The methodology presented in this study allows the prediction of active splicing factors in either cancer or any other condition by only using the information of transcript expression. This approach opens a wide range of possible studies to understand the splicing regulation of different conditions. A tutorial with the source code and databases is available at https://gitlab.com/fcarazo.m/sfprediction.

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