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A stochastic model for optimizing composite predictors based on gene expression profiles.

Murali Ramanathan
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Abstract

PURPOSE: This project was done to develop a mathematical model for optimizing composite predictors based on gene expression profiles from DNA arrays and proteomics. METHODS: The problem was amenable to a formulation and solution analogous to the portfolio optimization problem in mathematical finance: it requires the optimization of a quadratic function subject to linear constraints. The performance of the approach was compared to that of neighborhood analysis using a data set containing cDNA array-derived gene expression profiles from 14 multiple sclerosis patients receiving intramuscular inteferon-beta1a. RESULTS: The Markowitz portfolio model predicts that the covariance between genes can be exploited to construct an efficient composite. The model predicts that a composite is not needed for maximizing the mean value of a treatment effect: only a single gene is needed, but the usefulness of the effect measure may be compromised by high variability. The model optimized the composite to yield the highest mean for a given level of variability or the least variability for a given mean level. The choices that meet this optimization criteria lie on a curve of composite mean vs. composite variability plot referred to as the "efficient frontier." When a composite is constructed using the model, it outperforms the composite constructed using the neighborhood analysis method. CONCLUSIONS: The Markowitz portfolio model may find potential applications in constructing composite biomarkers and in the pharmacogenomic modeling of treatment effects derived from gene expression endpoints.

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AdultFemaleGene Expression ProfilingHumansLeukocytes, MononuclearMaleMiddle AgedModels, BiologicalPredictive Value of TestsStochastic ProcessesJournal ArticleResearch Support, Non-U.S. Gov't

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Murali Ramanathan. 2003. A stochastic model for optimizing composite predictors based on gene expression profiles.. https://doi.org/10.1023/a%3A1024450004215

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