MULTIPLE LATENT CLUSTERING MODEL FOR THE INFERENCE OF RNA LIFE-CYCLE KINETIC RATES FROM SEQUENCING DATA

• 成果类型: Article
• 署名作者: Mastrantonio, Gianluca; Bibbona, Enrico; Furlan, Mattia
• 署名单位: Polytechnic University of Turin; Istituto Italiano di Tecnologia - IIT; Center for Genomic Science IIT
• 刊物名称: ANNALS OF APPLIED STATISTICS
• ISSN/ISSBN: 1932-6157
• DOI: 10.1214/24-AOAS1945
• 发表日期: 2024
• 页码: 3467-3485
• 关键词: gene-expression; degradation dynamics; polymerase-ii; myc; tool

摘要

We propose a hierarchical Bayesian model to infer RNA synthesis, processing, and degradation rates from time-course RNA sequencing data, based on an ordinary differential equation system that models the RNA life cycle. We parametrize the latent kinetic rates, which rule the system, with a novel functional form and estimate their parameters through three Dirichlet process mixture models. Owing to the complexity of this approach, we are able to simultaneously perform inference, clustering, and model selection. We apply our method to investigate transcriptional and post-transcriptional responses of murine fibroblasts to the activation of the proto-oncogene Myc. Our approach uncovers simultaneous regulations of the rates, which had been largely missed in previous analyses of this biological system.