Application of the Cox Proportional Hazards Model for the Quantitative Analysis of LC-MS Proteomics Data

Date
2019
Authors
Arreola, Ivan
Han, David
Journal Title
Journal ISSN
Volume Title
Publisher
Office of the Vice President for Research
Abstract

Along with quantitative, analytical genomics, proteomics continues to be a growing field for determining the gene and cellular functions at the protein level. As the liquid chromatography mass spectrometryphy (LC-MS) experiments produce protein peak intensities data, statistical and computational techniques are required to conduct quantitative analytical proteomics. The LC-MS proteomics data often have large quantities of missing peak intensities due to censoring of the low-abundance spectral features. Because of this, the observed peak intensities from the LC-MS method are all positive, skewed, and often left-censored. The classical survival analysis methods are ideal to detect differentially expressed proteins among different groups. These methods include the non-parametric rank sum (RS) tests such as the Kolmogorov-Smirnov (KS) and Wilcoxon-Mann-Whitney (WMW) tests, parametric surivival models such as the accelerated failure time (AFT) model with popular lifetime distributions; log-normal (LN), log-logistic (LL), and Weibull (W) for modeling the peak intensity data. As an alternative approach, here we propose the Cox proportional hazards (PH) method, a popular semi-parametric model for modeling survival data. The proposed regression-based method allows for leniency on the hazard function by alleviating the requirements of distribution-specific hazard functions. With the hopes of gaining more insightful biological information for cellular functions at the protein level, the statistical properties of each method are investigated through a simulation study and an application to the Type I diabetes dataset.

Description
Keywords
Accelerated Failure Time Model, Cox Proportional Hazards Model, Liquid Chromatography Mass Spectrometry Proteomics, Survival Analysis, Type I Diabetes Mellitus
Citation
Department
Management Science and Statistics