Takeshi Emura (NCU) Joint work with Dr. Yi- Hau Chen and Dr. Hsuan -Yu Chen ( Sinica )
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Transcript of Takeshi Emura (NCU) Joint work with Dr. Yi- Hau Chen and Dr. Hsuan -Yu Chen ( Sinica )
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An extension of the compound covariate prediction under the Cox proportional hazard models
Emura , Chen & Chen [ 2012, PLoS ONE 7(10) ]
Takeshi Emura (NCU)Joint work with Dr. Yi-Hau Chen and Dr. Hsuan-Yu Chen (Sinica)
國立東華大學 應用數學系
2013/5/17
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Outline:1) Review: Survival data with high-dimensional covariates2) Review: Ridge regression3) Review: Compound covariate (CC) method4) Some theory on CC method5) Extension of the CC method Propose a new method6) Data example
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Lung cancer data from Chen et al. 2007 NEJMPatient ID Survival_Status100 alive , 47 months (censored)101 alive, 49 months (censored)102 death, 20 months109 death, 26110 alive, 39 (censored)113 alive, 35 (censored)115 alive, 45 (censored)116 death, 9128 death, 21.....365 alive, 5 months (censored)
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• Genetic information is useful in survival prediction:Breast cancer:(Jenssen et al., 2002; van de Vijver et al., 2002; van’t Veer et al., 2002; Zhao et al., 2011)
Lung cancer:(Beer et al., 2002; Chen et al., 2007; Shedden et al., 2008)
• Demand for statistical prediction methods adapted to high-dimensionality, especially on recent 10 years
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Hazard function:
• Cox proportional hazard model (Cox 1972)
•Partial likelihood estimator:
If , then If p > n, is not unique (infinitely many maxima)
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Idea of Ridge estimator(Hoerl & Kennard 1970)
Infinitely many solution in OLS
Unique nearest point to 0
Bayesian Interpretation :Hastile, Tibshirani, Friedman (2009)The Element of Statistical Learning
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• Penalized partial likelihood (Verweij & Houwelingen 1994)
)estimator Ridge(
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• Prediction by the Ridge estimator
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• Ridge regression (Cox-regression with L2 penalty)
Verve & van Howelingen(1994 Stat. Med.), Zhao et al. (2011 PLoS ONE)
• Lasso (Cox-regression with L1 penalty)
Gui & Li (2005 Bioinformatics), Segal (2006 Biostatistics)
• Gene selection via univariate Cox-regression
Jenssen et al. (2002 Nature Med.), Chen et al. (2007 NEJM), name but a few
• Others (Principal component, partial lease square, etc.)
Among above methods, ridge regression has the best performance in terms of survival prediction (Bovelstad et al., 2007; van Weieringen e al., 2009; Bovelstad and Borgan, 2011)
Existing methods for high-dimensional survival data
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Objectives of our study:
Propose a new prediction method that generalizes the so-called compound covariate prediction
Compound covariate prediction method *Previously used in medical context Tukey (1993 Controlled Clinical Trial), Beer et al. (2002 Nature Med.) Chen et al. (2007 NEJM), Radamacher et al (2002 J. of Theoretical Bio.) Matsui (2006 BMC Bioinformatics)
* Less known in statistical literature
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Compound covariate predictionStep1: For each gene , fit a univariate Cox model
Step2: A set of p regression coefficients
Remark: This is possible even when p > nStep 3: Compound covariate prediction
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Compound covariate method• is a univariate method to resolve the high
dimensionality
• empirically perform well in microarray studies
To motivate our proposal, we first give some theoretical results on the compound covariate method
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•Assumption: The Cox model holds with
at the true parameter
•Remark: Under the multivariate Cox model assumption, the univariate Cox model does not hold, i.e,
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•Univariate Cox model for each gene
is a misspecified model ( a working model ) Ref: Struthers & Kalbfleisch (1986) Misspecified proportional hazard models, Biometrika 73 pp.363-9.
•Univariate partial likelihood equation
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Remark I: If all genes are independent
Remark II:
Above results deduced from : Struthers & Kalbfleisch (1986 Biometrika) ; Bretagnolle & Huber-Carol(1988 Scand. JS)
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Proposed estimator•Univariate compound likelihood ( unique maxima )
•Multivariate likelihood ( infinitely many maxima when p > n )
•Idea: Mixture of univariate and multivariate likelihood
We call it “compound shrinkage estimator”
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• Proposition 2: (in our paper)
• Plug-in variance estimator
*Reasonable performance even when p > n.
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Numerical comparison Compare 4 methods1. Compound covariate (CC) estimator
2. Compound shrinkage (CS) estimator
3. Ridge estimator
4. Lasso estimator
* or is obtained by cross-validation (Verveij & Houwelingen 1993 Stat.Med.)
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estimators regressionCox univariate ˆ where,)ˆ,...,ˆ(ˆ1 jp β
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R compound.Cox package (Emura and Chen, 2012)
R penalized package (Goeman et al., 2012)
R penalized package
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}n1,...,i,ˆ{ ofmedian theis where
), prognosisPoor ( ˆ ; ) prognosis Good ( ˆ
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n=62, p=97 test set
•Data: Lung cancer data (Chen et al., 2007 NEJM)
LassoRidge
shrinkage compoundcovariate compound
ˆ
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} 62,...,1 { iix
n=63 , p=97Training set
Predict
Poor prognosisGood prognosis
n=125, p=672
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Survival curves for Poor vs. Good prognosis groups in n=62 testing data; p-value for Log-rank test
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Survival curves for Poor, Medium, Good prognosis groups for n=62 testing data; p-value for Log-rank trend test
Thank you for your attention