Analyzing Single-Molecule Protein Transportation Experiments via Hierarchical Hidden Markov Models

• 成果类型: Article
• 署名作者: Chen, Yang; Shen, Kuang; Shan, Shu-Ou; Kou, S. C.
• 署名单位: Harvard University; Massachusetts Institute of Technology (MIT); Whitehead Institute; California Institute of Technology
• 刊物名称: JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
• ISSN/ISSBN: 0162-1459
• DOI: 10.1080/01621459.2016.1140050
• 发表日期: 2016
• 页码: 951-966
• 关键词: signal recognition particle; srp rna; probabilistic functions; endoplasmic-reticulum; gtpase activation; complex; fret; translocation; distributions; mechanism

摘要

To maintain proper cellular functions, over 50% of proteins encoded in the genome need to be transported to cellular membranes. The molecular mechanism behind such a process, often referred to as protein targeting, is not well understood. Single-molecule experiments are designed to unveil the detailed mechanisms and reveal the functions of different molecular machineries involved in the process. The experimental data consist of hundreds of stochastic time traces from the fluorescence recordings of the experimental system. We introduce a Bayesian hierarchical model on top of hidden Markov models (HMMs) to analyze these data and use the statistical results to answer the biological questions. In addition to resolving the biological puzzles and delineating the regulating roles of different molecular complexes, our statistical results enable us to propose a more detailed mechanism for the late stages of the protein targeting process.