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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
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Integrative deep models for alternative splicing.

Anupama Jha1, Matthew R Gazzara1,2,3, Yoseph Barash1,2

  • 1Department of Computer and Information Science, School of Engineering, University of Pennsylvania, Philadelphia, PA, USA.

Bioinformatics (Oxford, England)
|September 9, 2017
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Summary
This summary is machine-generated.

This study enhances computational models for alternative splicing (AS) prediction by integrating diverse experimental data. The new framework improves accuracy in predicting splicing regulatory factors and offers biological insights.

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Area of Science:

  • Genomics
  • Computational Biology
  • Molecular Biology

Background:

  • Alternative splicing (AS) increases transcriptome complexity and aberrant splicing is linked to diseases.
  • Computational models (splicing codes) predict splicing outcomes from genomic sequence, but previously only used expression data.
  • Integrating diverse data sources can improve AS regulatory factor prediction.

Purpose of the Study:

  • To improve computational models for alternative splicing (AS) outcome prediction.
  • To integrate additional data sources for better AS regulatory factor predictions.
  • To develop a scalable framework for splicing code modeling.

Main Methods:

  • Compared Bayesian and Deep Neural Network models for AS prediction.
  • Developed a novel target function for exon skipping events to enhance model accuracy.
  • Utilized transfer learning to integrate noisy and incomplete data from CLIP-Seq, knockdown, and overexpression experiments.

Main Results:

  • The new target function significantly improved AS prediction accuracy.
  • The developed framework successfully integrated diverse experimental data, including CLIP-Seq and gene perturbation experiments.
  • Demonstrated prediction improvements and biological insights using mouse brain, muscle, and heart datasets.

Conclusions:

  • The proposed framework offers a scalable and integrative solution for improving splicing code modeling.
  • The study highlights the potential of integrating multiple data types for a deeper understanding of AS regulation.
  • The findings pave the way for more accurate predictions of AS regulatory factors.