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PCB: A pseudotemporal causality-based Bayesian approach to identify EMT-associated regulatory relationships of AS events and RBPs during breast cancer progression.

Abstract
During breast cancer metastasis, the developmental process epithelial-mesenchymal (EM) transition is abnormally activated. Transcriptional regulatory networks controlling EM transition are well-studied; however, alternative RNA splicing also plays a critical regulatory role during this process. Alternative splicing was proved to control the EM transition process, and RNA-binding proteins were determined to regulate alternative splicing. A comprehensive understanding of alternative splicing and the RNA-binding proteins that regulate it during EM transition and their dynamic impact on breast cancer remains largely unknown. To accurately study the dynamic regulatory relationships, time-series data of the EM transition process are essential. However, only cross-sectional data of epithelial and mesenchymal specimens are available. Therefore, we developed a pseudotemporal causality-based Bayesian (PCB) approach to infer the dynamic regulatory relationships between alternative splicing events and RNA-binding proteins. Our study sheds light on facilitating the regulatory network-based approach to identify key RNA-binding proteins or target alternative splicing events for the diagnosis or treatment of cancers. The data and code for PCB are available at: http://hkumath.hku.hk/~wkc/PCB(data+code).zip.
AuthorsLiangjie Sun, Yushan Qiu, Wai-Ki Ching, Pu Zhao, Quan Zou
JournalPLoS computational biology (PLoS Comput Biol) Vol. 19 Issue 3 Pg. e1010939 (03 2023) ISSN: 1553-7358 [Electronic] United States
PMID36930678 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright: © 2023 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Chemical References
  • RNA-Binding Proteins
Topics
  • Humans
  • Female
  • Breast Neoplasms (metabolism)
  • Bayes Theorem
  • Cross-Sectional Studies
  • Cell Line, Tumor
  • Neoplastic Processes
  • RNA-Binding Proteins (genetics, metabolism)
  • Alternative Splicing (genetics)
  • Epithelial-Mesenchymal Transition (genetics)

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