Grant Details
| Grant Number: |
5R37CA076404-17 Interpret this number |
| Primary Investigator: |
Lin, Xihong |
| Organization: |
Harvard University D/B/A Harvard School Of Public Health |
| Project Title: |
Statistical Methods for Correlated and High-Dimensional Biomedical Data |
| Fiscal Year: |
2013 |
Abstract
Correlated and high-dimensional data arise frequently in health sciences research, especially in cancer research. Correlated data arise in longitudinal studies and familial studies, while high-dimensional data have emerged in recent years as a consequence of the rapid advance of genomic and proteomic research. We propose in this application to develop nonparametric and semiparametric regression methods for clustered/longitudinal data and high-dimensional genomic and proteomic data. Specifically, we propose to develop (1) the kernel (spline) profile EM method for generalized semiparametric mixed models for clustered/longitudinal data; (2) nonparametric and semiparametric regression models for longitudinal data with dropouts; (3) the mixed model kernel machine method for generalized semiparametric regression models and semiparametric Cox models for the analysis of gene expression pathways and tag single nucleotide polymorphisms (SNPs) within a candidate gene, and the sparse kernel machine (SKM) method for selecting genes and tag SNPs from a large pool of genes or tag SNPs; (4) the joint modeling method using functional wavelet models and generalized semiparametric models for mass spectrometry proteomic data and disease outcomes. Asymptotic properties of the proposed methods will be investigated and simulation studies will be conducted to evaluate their finite sample performance. Efficient numerical algorithms and user-friendly statistical software will be developed, with the goal of disseminating these models and methods to health sciences researchers. In collaboration with biomedical investigators, we will apply the proposed models and methods to several motivating data sets on cancer research and other fields of research.
Publications
CpGFilter: model-based CpG probe filtering with replicates for epigenome-wide association studies.
Authors: Chen J.
, Just A.C.
, Schwartz J.
, Hou L.
, Jafari N.
, Sun Z.
, Kocher J.P.
, Baccarelli A.
, Lin X.
.
Source: Bioinformatics (oxford, England), 2016-02-01 00:00:00.0; 32(3), p. 469-71.
EPub date: 2016-02-01 00:00:00.0.
PMID: 26449931
Related Citations
Semiparametric frailty models for clustered failure time data.
Authors: Yu Z.
, Lin X.
, Tu W.
.
Source: Biometrics, 2012 Jun; 68(2), p. 429-36.
PMID: 22070739
Related Citations
Inverse probability of censoring weighted estimates of Kendall's ¿ for gap time analyses.
Authors: Lakhal-Chaieb L.
, Cook R.J.
, Lin X.
.
Source: Biometrics, 2010 Dec; 66(4), p. 1145-52.
PMID: 20337629
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Increased power for the analysis of label-free LC-MS/MS proteomics data by combining spectral counts and peptide peak attributes.
Authors: Dicker L.
, Lin X.
, Ivanov A.R.
.
Source: Molecular & Cellular Proteomics : Mcp, 2010 Dec; 9(12), p. 2704-18.
PMID: 20823122
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Powerful SNP-set analysis for case-control genome-wide association studies.
Authors: Wu M.C.
, Kraft P.
, Epstein M.P.
, Taylor D.M.
, Chanock S.J.
, Hunter D.J.
, Lin X.
.
Source: American Journal Of Human Genetics, 2010-06-11 00:00:00.0; 86(6), p. 929-42.
PMID: 20560208
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Bayesian inference in semiparametric mixed models for longitudinal data.
Authors: Li Y.
, Lin X.
, Müller P.
.
Source: Biometrics, 2010 Mar; 66(1), p. 70-8.
PMID: 19432777
Related Citations
Semiparametric modeling of longitudinal measurements and time-to-event data--a two-stage regression calibration approach.
Authors: Ye W.
, Lin X.
, Taylor J.M.
.
Source: Biometrics, 2008 Dec; 64(4), p. 1238-46.
PMID: 18261160
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Analysis of case-control age-at-onset data using a modified case-cohort method.
Authors: Nan B.
, Lin X.
.
Source: Biometrical Journal. Biometrische Zeitschrift, 2008 Apr; 50(2), p. 311-20.
PMID: 18318038
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A powerful and flexible multilocus association test for quantitative traits.
Authors: Kwee L.C.
, Liu D.
, Lin X.
, Ghosh D.
, Epstein M.P.
.
Source: American Journal Of Human Genetics, 2008 Feb; 82(2), p. 386-97.
PMID: 18252219
Related Citations
Estimation using penalized quasilikelihood and quasi-pseudo-likelihood in Poisson mixed models.
Authors: Lin X.
.
Source: Lifetime Data Analysis, 2007 Dec; 13(4), p. 533-44.
PMID: 18080833
Related Citations
Quantitative quality-assessment techniques to compare fractionation and depletion methods in SELDI-TOF mass spectrometry experiments.
Authors: Harezlak J.
, Wang M.
, Christiani D.
, Lin X.
.
Source: Bioinformatics (oxford, England), 2007-09-15 00:00:00.0; 23(18), p. 2441-8.
EPub date: 2007-09-15 00:00:00.0.
PMID: 17626063
Related Citations
Two-stage functional mixed models for evaluating the effect of longitudinal covariate profiles on a scalar outcome.
Authors: Zhang D.
, Lin X.
, Sowers M.
.
Source: Biometrics, 2007 Jun; 63(2), p. 351-62.
PMID: 17688488
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Missing covariates in longitudinal data with informative dropouts: bias analysis and inference.
Authors: Roy J.
, Lin X.
.
Source: Biometrics, 2005 Sep; 61(3), p. 837-46.
PMID: 16135036
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A varying-coefficient Cox model for the effect of age at a marker event on age at menopause.
Authors: Nan B.
, Lin X.
, Lisabeth L.D.
, Harlow S.D.
.
Source: Biometrics, 2005 Jun; 61(2), p. 576-83.
PMID: 16011707
Related Citations
Mixtures of varying coefficient models for longitudinal data with discrete or continuous nonignorable dropout.
Authors: Hogan J.W.
, Lin X.
, Herman B.
.
Source: Biometrics, 2004 Dec; 60(4), p. 854-64.
PMID: 15606405
Related Citations
A population pharmacokinetic model with time-dependent covariates measured with errors.
Authors: Li L.
, Lin X.
, Brown M.B.
, Gupta S.
, Lee K.H.
.
Source: Biometrics, 2004 Jun; 60(2), p. 451-60.
PMID: 15180671
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A tobit variance-component method for linkage analysis of censored trait data.
Authors: Epstein M.P.
, Lin X.
, Boehnke M.
.
Source: American Journal Of Human Genetics, 2003 Mar; 72(3), p. 611-20.
PMID: 12587095
Related Citations
Latent variable models for longitudinal data with multiple continuous outcomes.
Authors: Roy J.
, Lin X.
.
Source: Biometrics, 2000 Dec; 56(4), p. 1047-54.
PMID: 11129460
Related Citations
A scaled linear mixed model for multiple outcomes.
Authors: Lin X.
, Ryan L.
, Sammel M.
, Zhang D.
, Padungtod C.
, Xu X.
.
Source: Biometrics, 2000 Jun; 56(2), p. 593-601.
PMID: 10877322
Related Citations
Semiparametric regression for periodic longitudinal hormone data from multiple menstrual cycles.
Authors: Zhang D.
, Lin X.
, Sowers M.
.
Source: Biometrics, 2000 Mar; 56(1), p. 31-9.
PMID: 10783774
Related Citations