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Grant Details

Grant Number: 5R01CA204120-03 Interpret this number
Primary Investigator: Ma, Shuangge
Organization: Yale University
Project Title: Novel Methods for Identifying Genetic Interactions in Cancer Prognosis
Fiscal Year: 2018
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Abstract

? DESCRIPTION (provided by applicant): Project Summary In cancer prognosis, beyond the main effects of environmental/clinical (E) and genetic (G) risk factors, the interactions between G and E factors (G*E interactions) and those between G and G factors (G*G interactions) also play critical roles. The existing findings are insufficient, and there is a strong need for identifing more prognostic interactions. Most of the existing effort has been focused on data collection. In contrast, the development of effective analysis methods has been lagging behind. Compared to data collection, methodological development takes much less resources but is equally critical in making reliable findings. Most of the existing interaction analysis methods share the limitation of lacking robustness properties. In practice, data contamination and model mis-specification are not uncommon and can lead to severely biased model parameter estimation and false marker identification. The development of robust genetic interaction analysis methods is very limited. There are a few methods for case-control data, but they are not applicable to prognosis data. For prognosis data and interaction analysis, there is some very recent progress in quantile regression and rank-based methods, but the development has been limited and unsystematic. Last but not least, the existing robust methods have the common drawback of adopting ineffective marker selection techniques. Our group has been at the frontier of developing robust interaction analysis methods. Our statistical investigations and simulations have provided convincing evidences that the robust methods using the penalization technique outperform alternatives with significantly more accurate marker identification and model parameter estimation. In data analysis, important interactions missed by the existing analyses have been identified for multiple cancer types. However, we have also found that the scope of the existing studies needs to be significantly expanded in terms of both methodological development and data analysis. This project has been motivated by the importance of interactions in cancer prognosis and limitations of the existing studies. Our objectives are as follows. (Aim 1) Develop novel marginal analysis methods that are robust to data contamination and model mis-specification for identifying important interactions. (Aim 2) Develop novel joint analysis methods that are robust to data contamination and model mis-specification for identifying important interactions. (Aim 3) Develop tailored inference approaches to draw more definitive conclusions on the identified interactions. (Aim 4) Develop public R software and a dynamic project website. Identify prognostic interactions for multiple cancers. For the identified interactions, we will conduct extensive bioinformatic and statistical analysis, evaluations, and comparisons. With our unique expertise, extensive experiences, and promising preliminary studies, this project has a high likelihood of success.

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Publications

Assisted gene expression-based clustering with AWNCut.
Authors: Li Y. , Bie R. , Teran Hidalgo S.J. , Qin Y. , Wu M. , Ma S. .
Source: Statistics In Medicine, 2018-12-20 00:00:00.0; 37(29), p. 4386-4403.
EPub date: 2018-08-09 00:00:00.0.
PMID: 30094873
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Identification of cancer omics commonality and difference via community fusion.
Authors: Sun Y. , Jiang Y. , Li Y. , Ma S. .
Source: Statistics In Medicine, 2018-11-12 00:00:00.0; , .
EPub date: 2018-11-12 00:00:00.0.
PMID: 30421444
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Overlapping clustering of gene expression data using penalized weighted normalized cut.
Authors: Teran Hidalgo S.J. , Zhu T. , Wu M. , Ma S. .
Source: Genetic Epidemiology, 2018-10-09 00:00:00.0; , .
EPub date: 2018-10-09 00:00:00.0.
PMID: 30302823
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A Forward and Backward Stagewise Algorithm for Nonconvex Loss Functions with Adaptive Lasso.
Authors: Shi X. , Huang Y. , Huang J. , Ma S. .
Source: Computational Statistics & Data Analysis, 2018 Aug; 124, p. 235-251.
EPub date: 2018-03-28 00:00:00.0.
PMID: 30319163
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Robust identification of gene-environment interactions for prognosis using a quantile partial correlation approach.
Authors: Xu Y. , Wu M. , Zhang Q. , Ma S. .
Source: Genomics, 2018-07-16 00:00:00.0; , .
EPub date: 2018-07-16 00:00:00.0.
PMID: 30009922
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Dissecting gene-environment interactions: A penalized robust approach accounting for hierarchical structures.
Authors: Wu C. , Jiang Y. , Ren J. , Cui Y. , Ma S. .
Source: Statistics In Medicine, 2018-02-10 00:00:00.0; 37(3), p. 437-456.
EPub date: 2017-10-16 00:00:00.0.
PMID: 29034484
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Analysis of cancer gene expression data with an assisted robust marker identification approach.
Authors: Chai H. , Shi X. , Zhang Q. , Zhao Q. , Huang Y. , Ma S. .
Source: Genetic Epidemiology, 2017 Dec; 41(8), p. 779-789.
EPub date: 2017-09-14 00:00:00.0.
PMID: 28913902
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Integrative sparse principal component analysis of gene expression data.
Authors: Liu M. , Fan X. , Fang K. , Zhang Q. , Ma S. .
Source: Genetic Epidemiology, 2017 Dec; 41(8), p. 844-865.
EPub date: 2017-11-08 00:00:00.0.
PMID: 29114920
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Sparse boosting for high-dimensional survival data with varying coefficients.
Authors: Yue M. , Li J. , Ma S. .
Source: Statistics In Medicine, 2017-11-19 00:00:00.0; , .
EPub date: 2017-11-19 00:00:00.0.
PMID: 29152776
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Identifying gene-gene interactions using penalized tensor regression.
Authors: Wu M. , Huang J. , Ma S. .
Source: Statistics In Medicine, 2017-10-16 00:00:00.0; , .
EPub date: 2017-10-16 00:00:00.0.
PMID: 29034516
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Inferring gene regulatory relationships with a high-dimensional robust approach.
Authors: Zang Y. , Zhao Q. , Zhang Q. , Li Y. , Zhang S. , Ma S. .
Source: Genetic Epidemiology, 2017 Jul; 41(5), p. 437-454.
EPub date: 2017-05-02 00:00:00.0.
PMID: 28464328
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Accommodating missingness in environmental measurements in gene-environment interaction analysis.
Authors: Wu M. , Zang Y. , Zhang S. , Huang J. , Ma S. .
Source: Genetic Epidemiology, 2017-06-28 00:00:00.0; , .
EPub date: 2017-06-28 00:00:00.0.
PMID: 28657194
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Analyzing large datasets with bootstrap penalization.
Authors: Fang K. , Ma S. .
Source: Biometrical Journal. Biometrische Zeitschrift, 2017 Mar; 59(2), p. 358-376.
EPub date: 2016-11-21 00:00:00.0.
PMID: 27870109
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Focused Information Criterion and Model Averaging with Generalized Rank Regression.
Authors: Zhang Q. , Duan X. , Ma S. .
Source: Statistics & Probability Letters, 2017 Mar; 122, p. 11-19.
EPub date: 2016-10-31 00:00:00.0.
PMID: 28566799
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