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Journal of Computational Biology
A Patient-Gene Model for Temporal Expression Profiles in Clinical Studies
To cite this article:
Naftali Kaminski, Ziv Bar-Joseph.
Journal of Computational Biology.
April 2007,
14(3): 324-338.
doi:10.1089/cmb.2007.0001.
Naftali Kaminski Simmons Center for Interstitial Lung Disease, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania. Ziv Bar-Joseph Departments of Machine Learning, Carnegie Mellon University, Pittsburgh, Pennsylvania. Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania. Pharmacogenomics and clinical studies that measure the temporal expression levels of patients can identify important pathways and biomarkers that are activated during disease progression or in response to treatment. However, researchers face a number of challenges when trying to combine expression profiles from these patients. Unlike studies that rely on lab animals or cell lines, individuals vary in their baseline expression and in their response rate. In this paper we present a generative model for such data. Our model represents patient expression data using two levels, a gene level, which corresponds to a common response pattern, and a patient level, which accounts for the patient specific expression patterns and response rate. Using an EM algorithm, we infer the parameters of the model. We used our algorithm to analyze multiple sclerosis patient response to interferon-β. As we show, our algorithm was able to improve upon prior methods for combining patients data. In addition, our algorithm was able to correctly identify patient specific response patterns.  This paper was cited by:Constrained mixture estimation for analysis and robust classification of clinical time series I. G. Costa, A. Schonhuth, C. Hafemeister, A. Schliep Bioinformatics. Jul 2009, Vol. 25, No. 12: i6-i14 CrossRef Pairwise curve synchronization for functional data R. Tang, H.-G. Muller Biometrika. Dec 2008, Vol. 95, No. 4: 875-889 CrossRef Alignment and classification of time series gene expression in clinical studies T.-h. Lin, N. Kaminski, Z. Bar-Joseph Bioinformatics. Jun 2008, Vol. 24, No. 13: i147-i155 CrossRef
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