RT Journal
A1 Tapial, Javier
A1 Ha, Kevin C.H.
A1 Sterne-Weiler, Timothy
A1 Gohr, André
A1 Braunschweig, Ulrich
A1 Hermoso-Pulido, Antonio
A1 Quesnel-Vallières, Mathieu
A1 Permanyer, Jon
A1 Sodaei, Reza
A1 Marquez, Yamile
A1 Cozzuto, Luca
A1 Wang, Xinchen
A1 Gómez-Velázquez, Melisa
A1 Rayon, Teresa
A1 Manzanares, Miguel
A1 Ponomarenko, Julia
A1 Blencowe, Benjamin J.
A1 Irimia, Manuel
T1 An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms
JF Genome Research 
JO Genome Research 
YR 2017 
FD October 01 
VO 27 
IS 10 
SP 1759 
OP 1768 
DO 10.1101/gr.220962.117 
UL http://genome.cshlp.org/content/27/10/1759.abstract 
AB Alternative splicing (AS) generates remarkable regulatory and proteomic complexity in metazoans. However, the functions of most AS events are not known, and programs of regulated splicing remain to be identified. To address these challenges, we describe the Vertebrate Alternative Splicing and Transcription Database (VastDB), the largest resource of genome-wide, quantitative profiles of AS events assembled to date. VastDB provides readily accessible quantitative information on the inclusion levels and functional associations of AS events detected in RNA-seq data from diverse vertebrate cell and tissue types, as well as developmental stages. The VastDB profiles reveal extensive new intergenic and intragenic regulatory relationships among different classes of AS and previously unknown and conserved landscapes of tissue-regulated exons. Contrary to recent reports concluding that nearly all human genes express a single major isoform, VastDB provides evidence that at least 48% of multiexonic protein-coding genes express multiple splice variants that are highly regulated in a cell/tissue-specific manner, and that >18% of genes simultaneously express multiple major isoforms across diverse cell and tissue types. Isoforms encoded by the latter set of genes are generally coexpressed in the same cells and are often engaged by translating ribosomes. Moreover, they are encoded by genes that are significantly enriched in functions associated with transcriptional control, implying they may have an important and wide-ranging role in controlling cellular activities. VastDB thus provides an unprecedented resource for investigations of AS function and regulation.