A time-series DDP for functional proteomics profiles

Biometrics. 2012 Sep;68(3):859-68. doi: 10.1111/j.1541-0420.2011.01724.x. Epub 2012 Jan 5.

Abstract

Using a new type of array technology, the reverse phase protein array (RPPA), we measure time-course protein expression for a set of selected markers that are known to coregulate biological functions in a pathway structure. To accommodate the complex dependent nature of the data, including temporal correlation and pathway dependence for the protein markers, we propose a mixed effects model with temporal and protein-specific components. We develop a sequence of random probability measures (RPM) to account for the dependence in time of the protein expression measurements. Marginally, for each RPM we assume a Dirichlet process model. The dependence is introduced by defining multivariate beta distributions for the unnormalized weights of the stick-breaking representation. We also acknowledge the pathway dependence among proteins via a conditionally autoregressive model. Applying our model to the RPPA data, we reveal a pathway-dependent functional profile for the set of proteins as well as marginal expression profiles over time for individual markers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Biomarkers, Tumor / metabolism
  • Biometry
  • Cell Line, Tumor
  • Data Interpretation, Statistical
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Lapatinib
  • Linear Models
  • Markov Chains
  • Models, Statistical*
  • Monte Carlo Method
  • Multivariate Analysis
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism
  • Protein Array Analysis / statistics & numerical data*
  • Proteomics / statistics & numerical data*
  • Quinazolines / pharmacology
  • Signal Transduction / drug effects
  • Statistics, Nonparametric

Substances

  • Biomarkers, Tumor
  • Quinazolines
  • Lapatinib
  • ErbB Receptors