MTSplice predicts effects of genetic variants on tissue-specific splicing
Abstract 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-s...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-03-01
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| Series: | Genome Biology |
| Online Access: | https://doi.org/10.1186/s13059-021-02273-7 |
| Summary: | Abstract 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. |
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| ISSN: | 1474-760X |