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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
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COSSMO: predicting competitive alternative splice site selection using deep learning.

Hannes Bretschneider1,2, Shreshth Gandhi1, Amit G Deshwar1,3

  • 1Deep Genomics Inc, Toronto, Canada.

Bioinformatics (Oxford, England)
|June 29, 2018
PubMed
Summary
This summary is machine-generated.

We developed a new model, COSSMO, to predict alternative splicing events by accounting for competitive splice site selection. COSSMO accurately predicts splice site usage and learns key sequence motifs.

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Area of Science:

  • Genomics
  • Computational Biology
  • Molecular Biology

Background:

  • Alternative splicing is regulated by the competitive selection of splice sites.
  • The probability of splice site usage is influenced by neighboring site strengths.

Purpose of the Study:

  • To introduce the competitive splice site model (COSSMO) for predicting alternative splicing.
  • To model alternative splicing as a choice between 5' donor or 3' acceptor sites.

Main Methods:

  • Developed four distinct neural network architectures (CNN, communication layers, LSTM, ResNet) to learn motifs from sequence data.
  • Constructed a novel dataset using genome annotations and RNA-Seq data for model training.

Main Results:

  • COSSMO predicts the most frequent splice site with 70% accuracy on test data.
  • The model achieves an R2 of 0.6 in modeling the percent selected index (PSI) distribution.
  • Learned motifs correspond to consensus splice site sequences and known splicing factors.

Conclusions:

  • COSSMO effectively models competitive splice site selection.
  • The model demonstrates high accuracy in predicting splice site usage and PSI distribution.
  • COSSMO provides insights into splicing factor recognition and sequence motifs.