Statistical Applications in Genetics and Molecular Biology
Editor-in-Chief: Stumpf, Michael P.H.
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Most Downloaded Articles
- Sensitivity to prior specification in Bayesian genome-based prediction models by Lehermeier, Christina/ Wimmer, Valentin/ Albrecht, Theresa/ Auinger, Hans-Jürgen/ Gianola, Daniel/ Schmid, Volker J. and Schön, Chris-Carolin
- A Shrinkage Approach to Large-Scale Covariance Matrix Estimation and Implications for Functional Genomics by Schäfer, Juliane and Strimmer, Korbinian
- A General Framework for Weighted Gene Co-Expression Network Analysis by Zhang, Bin and Horvath, Steve
- Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments by Smyth, Gordon K
- Detecting Differential Expression in RNA-sequence Data Using Quasi-likelihood with Shrunken Dispersion Estimates by Lund, Steven P./ Nettleton, Dan/ McCarthy, Davis J. and Smyth, Gordon K.
Repeated Measures Semiparametric Regression Using Targeted Maximum Likelihood Methodology with Application to Transcription Factor Activity Discovery
1University of California, Berkeley
2University of California, Berkeley
Citation Information: Statistical Applications in Genetics and Molecular Biology. Volume 10, Issue 1, Pages 1–31, ISSN (Online) 1544-6115, DOI: 10.2202/1544-6115.1553, January 2011
- Published Online:
In longitudinal and repeated measures data analysis, often the goal is to determine the effect of a treatment or aspect on a particular outcome (e.g., disease progression). We consider a semiparametric repeated measures regression model, where the parametric component models effect of the variable of interest and any modification by other covariates. The expectation of this parametric component over the other covariates is a measure of variable importance. Here, we present a targeted maximum likelihood estimator of the finite dimensional regression parameter, which is easily estimated using standard software for generalized estimating equations.
The targeted maximum likelihood method provides double robust and locally efficient estimates of the variable importance parameters and inference based on the influence curve. We demonstrate these properties through simulation under correct and incorrect model specification, and apply our method in practice to estimating the activity of transcription factor (TF) over cell cycle in yeast. We specifically target the importance of SWI4, SWI6, MBP1, MCM1, ACE2, FKH2, NDD1, and SWI5.The semiparametric model allows us to determine the importance of a TF at specific time points by specifying time indicators as potential effect modifiers of the TF. Our results are promising, showing significant importance trends during the expected time periods. This methodology can also be used as a variable importance analysis tool to assess the effect of a large number of variables such as gene expressions or single nucleotide polymorphisms.