MTSplice predicts effects of genetic variants on tissue-specific splicing

Genome Biol. 2021 Mar 31;22(1):94. doi: 10.1186/s13059-021-02273-7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Autistic Disorder / genetics
  • Brain / metabolism
  • Computational Biology / methods*
  • Computational Biology / standards
  • Exons
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Variation*
  • Humans
  • Introns
  • Organ Specificity
  • Software*