MTSplice predicts effects of genetic variants on tissue-specific splicing

We develop the free and open-source model Multi-tissue Splicing (MTSplice) to predict the effects of genetic variants on splicing of cassette exons in 56 human tissues. MTSplice combines MMSplice, which models constitutive regulatory sequences, with a new neural network that models tissue-specific r...

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Bibliographic Details
Published in:Genome Biology 2021-03, Vol.22 (1), p.94-94, Article 94
Main Authors: Cheng, Jun, Çelik, Muhammed Hasan, Kundaje, Anshul, Gagneur, Julien
Format: Article
Language:English
Subjects:
Alternative Splicing
Autism
Autistic Disorder - genetics
Binding sites
Brain - metabolism
Computational Biology - methods
Computational Biology - standards
Datasets
Exons
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Genetic diversity
Genetic Variation
Humans
Introns
Method
Musculoskeletal system
Nervous system
Neural networks
Organ Specificity
Regulatory sequences
Software
Splicing
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Summary:We develop the free and open-source model Multi-tissue Splicing (MTSplice) to predict the effects of genetic variants on splicing of cassette exons in 56 human tissues. MTSplice combines MMSplice, which models constitutive regulatory sequences, with a new neural network that models tissue-specific regulatory sequences. MTSplice outperforms MMSplice on predicting tissue-specific variations associated with genetic variants in most tissues of the GTEx dataset, with largest improvements on brain tissues. Furthermore, MTSplice predicts that autism-associated de novo mutations are enriched for variants affecting splicing specifically in the brain. We foresee that MTSplice will aid interpreting variants associated with tissue-specific disorders.
ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-021-02273-7