A Pseudotemporal Causality-based Bayesian Approach to Identify EMT-associated Regulatory Relationships of AS events and RBPs During Breast Cancer Progression

Abstract

<p>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: <a href="http://hkumath.hku.hk/~wkc/PCB(data+code).zip">http://hkumath.hku.hk/~wkc/PCB(data+code).zip</a>.<br></p>