Reconstruction of composite regulator-target splicing networks from high-throughput transcriptome data

BMC Genomics

Research

Juan Valcarcel¹  Panagiotis Papasaikas²  A Javier Lopez³  Arvind Rao⁴  Peter Huggins⁵ 

[1] Centre for Genomic Regulation (CRG), c/Dr. Aiguader 88, 08003, Barcelona, Spain;Universitat Pompeu Fabra, Dr. Aiguader 88, 08003, Barcelona, Spain;Institució Catalana de Recerca i Estudis Avan¸cats (ICREA), c/Dr. Aiguader 88, 08003, Barcelona, Spain;Department of Biological Sciences, Carnegie Mellon University, 5000 Forbes Avenue, 15213, Pittsburgh, PA, USA;Centre for Genomic Regulation (CRG), c/Dr. Aiguader 88, 08003, Barcelona, Spain;Universitat Pompeu Fabra, Dr. Aiguader 88, 08003, Barcelona, Spain;Department of Biological Sciences, Carnegie Mellon University, 5000 Forbes Avenue, 15213, Pittsburgh, PA, USA;Department of Computational Biology, Carnegie Mellon University, 5000 Forbes Avenue, 15213, Pittsburgh, PA, USA;Department of Computational Biology, Carnegie Mellon University, 5000 Forbes Avenue, 15213, Pittsburgh, PA, USA;Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA;Department of Computational Biology, Carnegie Mellon University, 5000 Forbes Avenue, 15213, Pittsburgh, PA, USA;Robotics Institute, Carnegie Mellon University, 5000 Forbes Avenue, 15213, Pittsburgh, PA, USA;

关键词: Splicing;    Regulatory Network;    Module;    Exon;    Graphical Model;    mRNA Processing;    Splicing Factor;    Regulator;    Development;   

DOI  :  10.1186/1471-2164-16-S10-S7

来源: Springer

【 摘 要 】

We present a computational framework tailored for the modeling of the complex, dynamic relationships that are encountered in splicing regulation. The starting point is whole-genome transcriptomic data from high-throughput array or sequencing methods that are used to quantify gene expression and alternative splicing across multiple contexts. This information is used as input for state of the art methods for Graphical Model Selection in order to recover the structure of a composite network that simultaneously models exon co-regulation and their cognate regulators. Community structure detection and social network analysis methods are used to identify distinct modules and key actors within the network. As a proof of concept for our framework we studied the splicing regulatory network for Drosophila development using the publicly available modENCODE data. The final model offers a comprehensive view of the splicing circuitry that underlies fly development. Identified modules are associated with major developmental hallmarks including maternally loaded RNAs, onset of zygotic gene expression, transitions between life stages and sex differentiation. Within-module key actors include well-known developmental-specific splicing regulators from the literature while additional factors previously unassociated with developmental-specific splicing are also highlighted. Finally we analyze an extensive battery of Splicing Factor knock-down transcriptome data and demonstrate that our approach captures true regulatory relationships.

【 授权许可】

CC BY   
© Papasaikas et al.; 2015