The landscape of human mutually exclusive splicing.
Klas HatjeRaza-Ur RahmanRamon O VidalDominic SimmBjörn HammesfahrVikas BansalAshish RajputMichel Edwar MickaelTing SunStefan BonnMartin KollmarPublished in: Molecular systems biology (2017)
Mutually exclusive splicing of exons is a mechanism of functional gene and protein diversification with pivotal roles in organismal development and diseases such as Timothy syndrome, cardiomyopathy and cancer in humans. In order to obtain a first genomewide estimate of the extent and biological role of mutually exclusive splicing in humans, we predicted and subsequently validated mutually exclusive exons (MXEs) using 515 publically available RNA-Seq datasets. Here, we provide evidence for the expression of over 855 MXEs, 42% of which represent novel exons, increasing the annotated human mutually exclusive exome more than fivefold. The data provide strong evidence for the existence of large and multi-cluster MXEs in higher vertebrates and offer new insights into MXE evolution. More than 82% of the MXE clusters are conserved in mammals, and five clusters have homologous clusters in Drosophila Finally, MXEs are significantly enriched in pathogenic mutations and their spatio-temporal expression might predict human disease pathology.
Keyphrases
- rna seq
- endothelial cells
- single cell
- poor prognosis
- induced pluripotent stem cells
- pluripotent stem cells
- heart failure
- binding protein
- copy number
- transcription factor
- gene expression
- dna damage
- genome wide
- dna methylation
- young adults
- electronic health record
- case report
- deep learning
- dna repair
- lymph node metastasis
- genome wide identification