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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Splitpea: quantifying protein interaction network rewiring changes due to alternative splicing in cancer.

Ruth Dannenfelser1, Vicky Yao

  • 1Department of Computer Science, Rice University, Houston, TX 77005, USA.

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
|December 31, 2023
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Summary

This study introduces a computational method to analyze how alternative splicing affects protein-protein interactions (PPIs) in cancer. It identifies altered PPIs in cancer patients compared to normal tissues, aiding disease understanding.

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Area of Science:

  • Bioinformatics
  • Molecular Biology
  • Computational Biology

Background:

  • Protein-protein interactions (PPIs) are crucial for biological processes and disease mechanisms.
  • Alternative splicing diversifies protein function and remodels PPIs, impacting diseases like cancer.
  • Current PPI network approaches often neglect the impact of alternative splicing and isoform diversity.

Purpose of the Study:

  • To develop a computational approach for characterizing isoform-specific PPIs.
  • To analyze how alternative splicing events alter PPIs in cancer.
  • To compare cancer-specific PPIs with normal tissue PPIs.

Main Methods:

  • Utilized domain-domain interactions data.
  • Integrated differential exon usage data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project.
  • Developed a computational strategy to identify splicing-driven PPI alterations.

Main Results:

  • Characterized PPIs potentially disrupted or enhanced by alternative splicing events.
  • Provided a method to assess PPI changes in individual TCGA cancer samples against GTEx normal tissue.
  • Enabled the study of isoform-specific PPIs in the context of cancer.

Conclusions:

  • Alternative splicing significantly impacts PPI networks in cancer.
  • The developed computational approach can reveal disease-specific interaction changes.
  • Understanding isoform-specific PPIs is vital for deciphering disease biology.