Splitpea: quantifying protein interaction network rewiring changes due to alternative splicing in cancer

被引:0
|
作者
Dannenfelser, Ruth [1 ]
Yao, Vicky [1 ]
机构
[1] Rice Univ, Dept Comp Sci, Houston, TX 77005 USA
来源
BIOCOMPUTING 2024, PSB 2024 | 2024年
关键词
alternative splicing; protein-protein interaction networks; protein network rewiring; INTERACTION DATABASE; QUANTIFICATION; EXPANSION;
D O I
暂无
中图分类号
TP18 [人工智能理论];
学科分类号
081104 ; 0812 ; 0835 ; 1405 ;
摘要
Protein-protein interactions play an essential role in nearly all biological processes, and it has become increasingly clear that in order to better understand the fundamental processes that underlie disease, we must develop a strong understanding of both their context specificity (e.g., tissue-specificity) as well as their dynamic nature (e.g., how they respond to environmental changes). While network-based approaches have found much initial success in the application of protein-protein interactions (PPIs) towards systems-level explorations of biology, they often overlook the fact that large numbers of proteins undergo alternative splicing. Alternative splicing has not only been shown to diversify protein function through the generation of multiple protein isoforms, but also remodel PPIs and affect a wide range diseases, including cancer. Isoform-specific interactions are not well characterized, so we develop a computational approach that uses domain-domain interactions in concert with differential exon usage data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression project (GTEx). Using this approach, we can characterize PPIs likely disrupted or possibly even increased due to splicing events for individual TCGA cancer patient samples relative to a matched GTEx normal tissue background.
引用
收藏
页码:579 / 593
页数:15
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