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Grant Details

Grant Number: 2R01CA082659-10 Interpret this number
Primary Investigator: Lin, Danyu
Organization: Univ Of North Carolina Chapel Hill
Project Title: Statistical Methods in Cancer Research
Fiscal Year: 2008


Abstract

DESCRIPTION (provided by applicant): The broad, long-term objectives of this research are the developments of statistical methods for the designs and analysis of clinical and epidemiological cancer studies, with or without genetic components. The specific aims of this competing renewal application include: (1) exploring semiparametric linear transformation models for univariate and multivariate continuous response variables, (2) developing graphical and numerical techniques to assess model adequacy and predictive accuracy under semi- parametric transformation models for right censored failure time data, (3) studying semiparametric transformation models for the analysis of univariate and multivariate failure time data subject to interval censoring, (4) pursuing statistically efficient and computationally feasible procedures for the analysis of accelerated failure time and accelerated hazards models with right censored data, (5) investigating variance-components models for the joint linkage and association analysis of complex disease traits in family studies, (6) handling complex data structures (e.g., family data, selective genotyping, and correlated genetic and environmental factors with missing values) in the analysis of haplotype-disease associations, and (7) addressing the issue of population stratification in genetic association studies of unrelated individuals. All these problems are motivated by the principal investigator's applied research experiences and are highly relevant to current cancer research. The proposed solutions are based on likelihood and other sound statistical principles. The large-sample properties of the new estimators and test statistics will be established rigorously via modern empirical process theory and semiparametric efficiency theory. Efficient and reliable numerical algorithms will be developed to implement the inference procedures. The proposed methods will be evaluated extensively through computer simulation and be applied to a large number of cancer studies, most of which are carried out at the University of North Carolina. User-friendly software will be freely available to the general public. This research will not only significantly advance the fields of survival analysis, longitudinal data analysis and statistical genetics, but will also provide valuable new tools to cancer researchers. PUBLIC HEALTH RELEVANCE: The broad, long-term objectives of this research are the developments of statistical methods for the designs and analysis of clinical and epidemiological cancer studies, with or without genetic components.



Publications

Genetic analyses of diverse populations improves discovery for complex traits.
Authors: Wojcik G.L. , Graff M. , Nishimura K.K. , Tao R. , Haessler J. , Gignoux C.R. , Highland H.M. , Patel Y.M. , Sorokin E.P. , Avery C.L. , et al. .
Source: Nature, 2019 Jun; 570(7762), p. 514-518.
EPub date: 2019-06-19 00:00:00.0.
PMID: 31217584
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Semiparametric Regression Analysis of Multiple Right- and Interval-Censored Events.
Authors: Gao F. , Zeng D. , Couper D. , Lin D.Y. .
Source: Journal Of The American Statistical Association, 2019; 114(527), p. 1232-1240.
EPub date: 2018-08-17 00:00:00.0.
PMID: 31588157
Related Citations

Semiparametric regression analysis of interval-censored data with informative dropout.
Authors: Gao F. , Zeng D. , Lin D.Y. .
Source: Biometrics, 2018-06-05 00:00:00.0; , .
EPub date: 2018-06-05 00:00:00.0.
PMID: 29870067
Related Citations

Efficient ℓ0 -norm feature selection based on augmented and penalized minimization.
Authors: Li X. , Xie S. , Zeng D. , Wang Y. .
Source: Statistics In Medicine, 2018-02-10 00:00:00.0; 37(3), p. 473-486.
EPub date: 2017-10-30 00:00:00.0.
PMID: 29082539
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Efficient Estimation for Semiparametric Structural Equation Models With Censored Data.
Authors: Wong K.Y. , Zeng D. , Lin D.Y. .
Source: Journal Of The American Statistical Association, 2018; 113(522), p. 893-905.
EPub date: 2018-06-06 00:00:00.0.
PMID: 30083023
Related Citations

Maximum likelihood estimation for semiparametric regression models with multivariate interval-censored data.
Authors: Zeng D. , Gao F. , Lin D.Y. .
Source: Biometrika, 2017 Sep; 104(3), p. 505-525.
EPub date: 2017-07-12 00:00:00.0.
PMID: 29391606
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Synthex: A Synthetic-normal-based Dna Sequencing Tool For Copy Number Alteration Detection And Tumor Heterogeneity Profiling
Authors: Silva G.O. , Siegel M.B. , Mose L.E. , Parker J.S. , Sun W. , Perou C.M. , Chen M. .
Source: Genome Biology, 2017-04-08 00:00:00.0; 18(1), p. 66.
PMID: 28390427
Related Citations

Efficient Estimation Of Semiparametric Transformation Models For The Cumulative Incidence Of Competing Risks
Authors: Mao L. , Lin D.Y. .
Source: Journal Of The Royal Statistical Society. Series B, Statistical Methodology, 2017 Mar; 79(2), p. 573-587.
PMID: 28239261
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Semiparametric Regression Analysis Of Interval-censored Competing Risks Data
Authors: Mao L. , Lin D.Y. , Zeng D. .
Source: Biometrics, 2017-02-17 00:00:00.0; , .
PMID: 28211951
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Premeta: A Tool To Facilitate Meta-analysis Of Rare-variant Associations
Authors: Tang Z.Z. , Bunn P. , Tao R. , Liu Z. , Lin D.Y. .
Source: Bmc Genomics, 2017-02-14 00:00:00.0; 18(1), p. 160.
PMID: 28196472
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Efficient Semiparametric Inference Under Two-Phase Sampling, With Applications to Genetic Association Studies.
Authors: Tao R. , Zeng D. , Lin D.Y. .
Source: Journal Of The American Statistical Association, 2017; 112(520), p. 1468-1476.
EPub date: 2017-02-28 00:00:00.0.
PMID: 29479125
Related Citations

Simultaneous inference on treatment effects in survival studies with factorial designs.
Authors: Lin D.Y. , Gong J. , Gallo P. , Bunn P.H. , Couper D. .
Source: Biometrics, 2016 Dec; 72(4), p. 1078-1085.
PMID: 26991149
Related Citations

On confidence intervals for the hazard ratio in randomized clinical trials.
Authors: Lin D.Y. , Dai L. , Cheng G. , Sailer M.O. .
Source: Biometrics, 2016 Dec; 72(4), p. 1098-1102.
PMID: 27123760
Related Citations

Quantile Regression Models For Current Status Data
Authors: Ou F.S. , Zeng D. , Cai J. .
Source: Journal Of Statistical Planning And Inference, 2016 Nov; 178, p. 112-127.
PMID: 27994307
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Variable selection for case-cohort studies with failure time outcome.
Authors: Ni A.I. , Cai J. , Zeng D. .
Source: Biometrika, 2016 Sep; 103(3), p. 547-562.
EPub date: 2016-08-10 00:00:00.0.
PMID: 28529347
Related Citations

Rare variant associations with waist-to-hip ratio in European-American and African-American women from the NHLBI-Exome Sequencing Project.
Authors: Kan M. , Auer P.L. , Wang G.T. , Bucasas K.L. , Hooker S. , Rodriguez A. , Li B. , Ellis J. , Adrienne Cupples L. , Ida Chen Y.D. , et al. .
Source: European Journal Of Human Genetics : Ejhg, 2016 Aug; 24(8), p. 1181-7.
PMID: 26757982
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Estimating DNA methylation levels by joint modeling of multiple methylation profiles from microarray data.
Authors: Wang T. , Chen M. , Zhao H. .
Source: Biometrics, 2016 Jun; 72(2), p. 354-63.
PMID: 26433612
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Posterior Contraction Rates of the Phylogenetic Indian Buffet Processes.
Authors: Chen M. , Gao C. , Zhao H. .
Source: Bayesian Analysis, 2016 Jun; 11(2), p. 477-497.
PMID: 27087886
Related Citations

Maximum likelihood estimation for semiparametric transformation models with interval-censored data.
Authors: Zeng D. , Mao L. , Lin D.Y. .
Source: Biometrika, 2016 Jun; 103(2), p. 253-271.
PMID: 27279656
Related Citations

Sparse meta-analysis with high-dimensional data.
Authors: He Q. , Zhang H.H. , Avery C.L. , Lin D.Y. .
Source: Biostatistics (oxford, England), 2016 Apr; 17(2), p. 205-20.
PMID: 26395907
Related Citations

Semiparametric regression for the weighted composite endpoint of recurrent and terminal events.
Authors: Mao L. , Lin D.Y. .
Source: Biostatistics (oxford, England), 2016 Apr; 17(2), p. 390-403.
PMID: 26668069
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Global copy number profiling of cancer genomes.
Authors: Wang X. , Chen M. , Yu X. , Pornputtapong N. , Chen H. , Zhang N.R. , Powers R.S. , Krauthammer M. .
Source: Bioinformatics (oxford, England), 2016-03-15 00:00:00.0; 32(6), p. 926-8.
EPub date: 2016-03-15 00:00:00.0.
PMID: 26576652
Related Citations

CHANGE POINT ANALYSIS OF HISTONE MODIFICATIONS REVEALS EPIGENETIC BLOCKS LINKING TO PHYSICAL DOMAINS.
Authors: Chen M. , Lin H. , Zhao H. .
Source: The Annals Of Applied Statistics, 2016 Mar; 10(1), p. 506-526.
PMID: 27231496
Related Citations

Asymptotically Normal and Efficient Estimation of Covariate-Adjusted Gaussian Graphical Model.
Authors: Chen M. , Ren Z. , Zhao H. , Zhou H. .
Source: Journal Of The American Statistical Association, 2016 Mar; 111(513), p. 394-406.
PMID: 27499564
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Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk.
Authors: Yu B. , Pulit S.L. , Hwang S.J. , Brody J.A. , Amin N. , Auer P.L. , Bis J.C. , Boerwinkle E. , Burke G.L. , Chakravarti A. , et al. .
Source: Circulation. Cardiovascular Genetics, 2016 Feb; 9(1), p. 64-70.
PMID: 26658788
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Personalized Dose Finding Using Outcome Weighted Learning
Authors: Chen G. , Zeng D. , Kosorok M.R. .
Source: Journal Of The American Statistical Association, 2016; 111(516), p. 1509-1521.
PMID: 28255189
Related Citations

Multiple kernel learning with random effects for predicting longitudinal outcomes and data integration.
Authors: Chen T. , Zeng D. , Wang Y. .
Source: Biometrics, 2015 Dec; 71(4), p. 918-28.
PMID: 26177419
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Efficient Estimation of Nonparametric Genetic Risk Function with Censored Data.
Authors: Wang Y. , Liang B. , Tong X. , Marder K. , Bressman S. , Orr-Urtreger A. , Giladi N. , Zeng D. .
Source: Biometrika, 2015-09-01 00:00:00.0; 102(3), p. 515-532.
PMID: 26412864
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Allele-specific copy-number discovery from whole-genome and whole-exome sequencing.
Authors: Wang W. , Wang W. , Sun W. , Crowley J.J. , Szatkiewicz J.P. .
Source: Nucleic Acids Research, 2015-08-18 00:00:00.0; 43(14), p. e90.
EPub date: 2015-08-18 00:00:00.0.
PMID: 25883151
Related Citations

Meta-analysis for Discovering Rare-Variant Associations: Statistical Methods and Software Programs.
Authors: Tang Z.Z. , Lin D.Y. .
Source: American Journal Of Human Genetics, 2015-07-02 00:00:00.0; 97(1), p. 35-53.
EPub date: 2015-07-02 00:00:00.0.
PMID: 26094574
Related Citations

Analysis of Sequence Data Under Multivariate Trait-Dependent Sampling.
Authors: Tao R. , Zeng D. , Franceschini N. , North K.E. , Boerwinkle E. , Lin D.Y. .
Source: Journal Of The American Statistical Association, 2015-06-01 00:00:00.0; 110(510), p. 560-572.
PMID: 26366025
Related Citations

On random-effects meta-analysis.
Authors: Zeng D. , Lin D.Y. .
Source: Biometrika, 2015 Jun; 102(2), p. 281-294.
PMID: 26688589
Related Citations

Quantifying the average of the time-varying hazard ratio via a class of transformations.
Authors: Chen Q. , Zeng D. , Ibrahim J.G. , Chen M.H. , Pan Z. , Xue X. .
Source: Lifetime Data Analysis, 2015 Apr; 21(2), p. 259-79.
PMID: 25073864
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Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways.
Authors: Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium .
Source: Nature Neuroscience, 2015 Feb; 18(2), p. 199-209.
PMID: 25599223
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Integrative analysis of sequencing and array genotype data for discovering disease associations with rare mutations.
Authors: Hu Y.J. , Li Y. , Auer P.L. , Lin D.Y. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2015-01-27 00:00:00.0; 112(4), p. 1019-24.
EPub date: 2015-01-27 00:00:00.0.
PMID: 25583502
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Genetic variation in estrogen and progesterone pathway genes and breast cancer risk: an exploration of tumor subtype-specific effects.
Authors: Nyante S.J. , Gammon M.D. , Kaufman J.S. , Bensen J.T. , Lin D.Y. , Barnholtz-Sloan J.S. , Hu Y. , He Q. , Luo J. , Millikan R.C. .
Source: Cancer Causes & Control : Ccc, 2015 Jan; 26(1), p. 121-31.
PMID: 25421376
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Proper Use of Allele-Specific Expression Improves Statistical Power for cis-eQTL Mapping with RNA-Seq Data.
Authors: Hu Y.J. , Sun W. , Tzeng J.Y. , Perou C.M. .
Source: Journal Of The American Statistical Association, 2015; 110(511), p. 962-974.
PMID: 26568645
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IsoDOT Detects Differential RNA-isoform Expression/Usage with respect to a Categorical or Continuous Covariate with High Sensitivity and Specificity.
Authors: Sun W. , Liu Y. , Crowley J.J. , Chen T.H. , Zhou H. , Chu H. , Huang S. , Kuan P.F. , Li Y. , Miller D.R. , et al. .
Source: Journal Of The American Statistical Association, 2015; 110(511), p. 975-986.
PMID: 26617424
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Reinforcement Learning Trees.
Authors: Zhu R. , Zeng D. , Kosorok M.R. .
Source: Journal Of The American Statistical Association, 2015; 110(512), p. 1770-1784.
PMID: 26903687
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Genetic association analysis under complex survey sampling: the Hispanic Community Health Study/Study of Latinos.
Authors: Lin D.Y. , Tao R. , Kalsbeek W.D. , Zeng D. , Gonzalez F. , Fernández-Rhodes L. , Graff M. , Koch G.G. , North K.E. , Heiss G. .
Source: American Journal Of Human Genetics, 2014-12-04 00:00:00.0; 95(6), p. 675-88.
PMID: 25480034
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Bayesian design of superiority clinical trials for recurrent events data with applications to bleeding and transfusion events in myelodyplastic syndrome.
Authors: Chen M.H. , Ibrahim J.G. , Zeng D. , Hu K. , Jia C. .
Source: Biometrics, 2014 Dec; 70(4), p. 1003-13.
PMID: 25041037
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Inactivating mutations in NPC1L1 and protection from coronary heart disease.
Authors: Myocardial Infarction Genetics Consortium Investigators , Stitziel N.O. , Won H.H. , Morrison A.C. , Peloso G.M. , Do R. , Lange L.A. , Fontanillas P. , Gupta N. , Duga S. , et al. .
Source: The New England Journal Of Medicine, 2014-11-27 00:00:00.0; 371(22), p. 2072-82.
EPub date: 2014-11-27 00:00:00.0.
PMID: 25390462
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Sample size/power calculation for stratified case-cohort design.
Authors: Hu W. , Cai J. , Zeng D. .
Source: Statistics In Medicine, 2014-10-15 00:00:00.0; 33(23), p. 3973-85.
EPub date: 2014-10-15 00:00:00.0.
PMID: 24889145
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A Likelihood-Based Framework for Association Analysis of Allele-Specific Copy Numbers.
Authors: Hu Y.J. , Lin D.Y. , Sun W. , Zeng D. .
Source: Journal Of The American Statistical Association, 2014 Oct; 109(508), p. 1533-1545.
PMID: 25663726
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Targeted Local Support Vector Machine for Age-Dependent Classification.
Authors: Chen T. , Wang Y. , Chen H. , Marder K. , Zeng D. .
Source: Journal Of The American Statistical Association, 2014-09-01 00:00:00.0; 109(507), p. 1174-1187.
PMID: 25284918
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Loss-of-function mutations in APOC3, triglycerides, and coronary disease.
Authors: TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute , Crosby J. , Peloso G.M. , Auer P.L. , Crosslin D.R. , Stitziel N.O. , Lange L.A. , Lu Y. , Tang Z.Z. , Zhang H. , et al. .
Source: The New England Journal Of Medicine, 2014-07-03 00:00:00.0; 371(1), p. 22-31.
EPub date: 2014-07-03 00:00:00.0.
PMID: 24941081
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Meta-analysis of sequencing studies with heterogeneous genetic associations.
Authors: Tang Z.Z. , Lin D.Y. .
Source: Genetic Epidemiology, 2014 Jul; 38(5), p. 389-401.
PMID: 24799183
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Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol.
Authors: Lange L.A. , Hu Y. , Zhang H. , Xue C. , Schmidt E.M. , Tang Z.Z. , Bizon C. , Lange E.M. , Smith J.D. , Turner E.H. , et al. .
Source: American Journal Of Human Genetics, 2014-02-06 00:00:00.0; 94(2), p. 233-45.
PMID: 24507775
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Bayesian gamma frailty models for survival data with semi-competing risks and treatment switching.
Authors: Zhang Y. , Chen M.H. , Ibrahim J.G. , Zeng D. , Chen Q. , Pan Z. , Xue X. .
Source: Lifetime Data Analysis, 2014 Jan; 20(1), p. 76-105.
PMID: 23543121
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Survival analysis with incomplete genetic data.
Authors: Lin D.Y. .
Source: Lifetime Data Analysis, 2014 Jan; 20(1), p. 16-22.
PMID: 23722305
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