BAYESIAN APPROACHES TO MODEL SELECTION FOR SURVIVAL DATA

Summary

Principal Investigator: Joseph G Ibrahim
Abstract: DESCRIPTION (provided by applicant): In this proposal, we develop Bayesian methodology for high dimensional genomic data. The overarching theme in this proposal is that we develop several novel statistical methods for motif discovery in genomic sequence data. Chromatin Immunoprecipitation microarray (ChIP-chip) data allows the direct identification of transcription factor binding sites that are active in particular biological states. Jointly modeling array intensities and DNA sequence will lead to more accurate estimation of binding sites. We develop these joint models to account for multiple motifs and varied relationships between binding sites and array intensities. We also propose a novel joint model framework for direct estimation of a motif using gene expression and the DNA sequence that bypasses computationally expensive motif selection procedures. Chromatin structure, in the form of positioning of nucleosomes in DNA, has long been known to play a huge role in protein-DNA binding, however, a quantitative assessment of this role has not been available until very recently. Taking advantage of the increasing availability of accurate experimental data assessing chromatin features, we propose a novel Bayesian statistical model framework for improving motif detection through integration of nucleosome positioning and genomic sequence data. Alternative splicing of mRNA greatly expands the functional repertoire of many genes in the mammalian genome by including or excluding the exons making up the genetic coding sequence. Standard gene expression arrays fail to capture the variability of the exon composition of mRNA species, but rather give a crude measure of overall gene expression. We propose a method that detects over-representation of specific splice junctions in different biological states while adjusting for overall gene expression. The advent of high-throughput genomic technologies has ushered in a new data-driven era, allowing the ability to measure biological activity on a genome-wide scale. Chromatin Immunoprecipitation (ChIP), histone modification, and FAIRE for example are procedures that benefited from this technology, allowing one to determine relative enrichment for their isolated fragments genome wide. The recent development of Next generation sequencing (NGS) platforms offers greater dynamic range, resolution, and genomic coverage in measuring relative enrichment of DNA fragments compared to microarrays. We develop classes of statistical mixture models based on the zero-inflated negative binomial distribution to model such count data and develop an R software package called Zero-Inflated Negative Binomial Algorithm (ZINBA) to carry out the peak calling for a given dataset. 1
Funding Period: 1996-03-01 - 2015-08-31
more information: NIH RePORT

Top Publications

  1. ncbi Joint modeling of longitudinal and survival data with missing and left-censored time-varying covariates
    Qingxia Chen
    Department of Biostatistics, Vanderbilt University, Nashville, TN, 37232, U S A Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, 37232, U S A
    Stat Med 33:4560-76. 2014
  2. pmc Microwave and magnetic (M(2) ) proteomics of the experimental autoimmune encephalomyelitis animal model of multiple sclerosis
    Itay Raphael
    Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA
    Electrophoresis 33:3810-9. 2012
  3. pmc MiR-351 transiently increases during muscle regeneration and promotes progenitor cell proliferation and survival upon differentiation
    Yongxin Chen
    Department of Pathology, University of Texas Health Science Center, San Antonio, Texas, USA
    Physiol Genomics 44:1042-51. 2012
  4. pmc Meta-analysis methods and models with applications in evaluation of cholesterol-lowering drugs
    Ming Hui Chen
    Department of Statistics, University of Connecticut, Storrs, CT, USA
    Stat Med 31:3597-616. 2012
  5. pmc Projection regression models for multivariate imaging phenotype
    Ja an Lin
    Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Genet Epidemiol 36:631-41. 2012
  6. pmc Missing data in clinical studies: issues and methods
    Joseph G Ibrahim
    Department of Biostatistics, University of North Carolina, CB 7420, Chapel Hill, NC 27599, USA
    J Clin Oncol 30:3297-303. 2012
  7. pmc A prognostic signature of defective p53-dependent G1 checkpoint function in melanoma cell lines
    Craig Carson
    Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Pigment Cell Melanoma Res 25:514-26. 2012
  8. pmc The TBX21 transcription factor T-1993C polymorphism is associated with decreased IFN-γ and IL-4 production by primary human lymphocytes
    K M Fyall
    Department of Dermatology, University of North Carolina, Chapel Hill, NC USA
    Hum Immunol 73:673-6. 2012
  9. pmc Bayesian inference of the fully specified subdistribution model for survival data with competing risks
    Miaomiao Ge
    Clinical Bio Statistics, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT 06877, USA
    Lifetime Data Anal 18:339-63. 2012
  10. pmc Bayesian influence measures for joint models for longitudinal and survival data
    Hongtu Zhu
    Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7420, USA
    Biometrics 68:954-64. 2012

Detail Information

Publications73

  1. ncbi Joint modeling of longitudinal and survival data with missing and left-censored time-varying covariates
    Qingxia Chen
    Department of Biostatistics, Vanderbilt University, Nashville, TN, 37232, U S A Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, 37232, U S A
    Stat Med 33:4560-76. 2014
    ..A Bayesian analysis is conducted on the MACS data using the proposed joint model. The proposed method is shown to improve the precision of estimates when compared with alternative methods...
  2. pmc Microwave and magnetic (M(2) ) proteomics of the experimental autoimmune encephalomyelitis animal model of multiple sclerosis
    Itay Raphael
    Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA
    Electrophoresis 33:3810-9. 2012
    ....
  3. pmc MiR-351 transiently increases during muscle regeneration and promotes progenitor cell proliferation and survival upon differentiation
    Yongxin Chen
    Department of Pathology, University of Texas Health Science Center, San Antonio, Texas, USA
    Physiol Genomics 44:1042-51. 2012
    ....
  4. pmc Meta-analysis methods and models with applications in evaluation of cholesterol-lowering drugs
    Ming Hui Chen
    Department of Statistics, University of Connecticut, Storrs, CT, USA
    Stat Med 31:3597-616. 2012
    ..The proposed methodology is quite general and can be applied in any meta-analysis setting for a wide range of scientific applications and therefore offers new analytic methods of clinical importance...
  5. pmc Projection regression models for multivariate imaging phenotype
    Ja an Lin
    Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Genet Epidemiol 36:631-41. 2012
    ..Simulation studies and an imaging genetic dataset are used to examine the finite sample performance of the PRM...
  6. pmc Missing data in clinical studies: issues and methods
    Joseph G Ibrahim
    Department of Biostatistics, University of North Carolina, CB 7420, Chapel Hill, NC 27599, USA
    J Clin Oncol 30:3297-303. 2012
    ..Although the main area of application discussed here is cancer, the issues and methods we discuss apply to any type of study...
  7. pmc A prognostic signature of defective p53-dependent G1 checkpoint function in melanoma cell lines
    Craig Carson
    Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Pigment Cell Melanoma Res 25:514-26. 2012
    ..Thus, p53 function, radio-sensitivity, and metastatic spread may be estimated in melanomas from a signature of gene expression...
  8. pmc The TBX21 transcription factor T-1993C polymorphism is associated with decreased IFN-γ and IL-4 production by primary human lymphocytes
    K M Fyall
    Department of Dermatology, University of North Carolina, Chapel Hill, NC USA
    Hum Immunol 73:673-6. 2012
    ..We found that the TBX21 promoter polymorphism T-1993C is associated with a significant decrease in IL-4 and IFN-γ production by stimulated primary human lymphocytes from healthy participants...
  9. pmc Bayesian inference of the fully specified subdistribution model for survival data with competing risks
    Miaomiao Ge
    Clinical Bio Statistics, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT 06877, USA
    Lifetime Data Anal 18:339-63. 2012
    ..The proposed methodology is applied to analyze a real dataset from a prostate cancer study in detail...
  10. pmc Bayesian influence measures for joint models for longitudinal and survival data
    Hongtu Zhu
    Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7420, USA
    Biometrics 68:954-64. 2012
    ..Simulation studies and a real data set are used to highlight the broad spectrum of applications for our Bayesian influence methods...
  11. pmc Bayesian lasso for semiparametric structural equation models
    Ruixin Guo
    Department of Biostatistics, University of North Carolina at Chapel Hill, USA
    Biometrics 68:567-77. 2012
    ..Results demonstrate that our method can accurately estimate the unknown parameters and correctly identify the true underlying model...
  12. pmc Bayesian meta-experimental design: evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes
    Joseph G Ibrahim
    Department of Biostatistics, University of North Carolina, McGavran Greenberg Hall, Chapel Hill, North Carolina 27599, USA
    Biometrics 68:578-86. 2012
    ..The proposed methodology is applied to the design of a phase 2/3 development program including a noninferiority clinical trial for CV risk assessment in T2DM studies...
  13. pmc ZINBA integrates local covariates with DNA-seq data to identify broad and narrow regions of enrichment, even within amplified genomic regions
    Naim U Rashid
    Department of Biostatistics, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Genome Biol 12:R67. 2011
    ..ZINBA provides a single unified framework for analyzing DNA-seq experiments in challenging genomic contexts...
  14. pmc Genotype-guided tamoxifen dosing increases active metabolite exposure in women with reduced CYP2D6 metabolism: a multicenter study
    William J Irvin
    University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    J Clin Oncol 29:3232-9. 2011
    ....
  15. ncbi Maximum likelihood estimation in generalized linear models with multiple covariates subject to detection limits
    Ryan C May
    Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
    Stat Med 30:2551-61. 2011
    ..Through simulation studies, we show that the proposed approach can lead to a significant reduction in variance for parameter estimates in these models, improving the power of such studies...
  16. pmc Timeless functions independently of the Tim-Tipin complex to promote sister chromatid cohesion in normal human fibroblasts
    Stephanie L Smith-Roe
    University of North Carolina at Chapel Hill, Chapel Hill, NC USA
    Cell Cycle 10:1618-24. 2011
    ..A better understanding of how Timeless, Tipin and Claspin promote SCC will elucidate non-checkpoint functions of these proteins at DNA replication forks and inform models of the establishment of SCC...
  17. pmc Bayesian methods in clinical trials: a Bayesian analysis of ECOG trials E1684 and E1690
    Joseph G Ibrahim
    Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA
    BMC Med Res Methodol 12:183. 2012
    ..The analyses of E1684 and E1690 were carried out separately when the results were published, and there were no further analyses trying to perform a single analysis of the combined trials...
  18. pmc Multivariate recurrent events in the presence of multivariate informative censoring with applications to bleeding and transfusion events in myelodysplastic syndrome
    Donglin Zeng
    a Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA
    J Biopharm Stat 24:429-42. 2014
    ..We utilize the MDS clinical trial data to illustrate our proposed methodology. We also conduct a number of simulations to examine the performance of the proposed model...
  19. pmc Bayesian sequential meta-analysis design in evaluating cardiovascular risk in a new antidiabetic drug development program
    Ming Hui Chen
    Department of Statistics, University of Connecticut, Storrs, Connecticut 06269, U S A
    Stat Med 33:1600-18. 2014
    ..We apply the proposed methodology to the design of a hypothetical antidiabetic drug development program for evaluating cardiovascular risk...
  20. pmc Posterior predictive Bayesian phylogenetic model selection
    Paul O Lewis
    Department of Ecology and Evolutionary Biology, University of Connecticut, 75 N Eagleville Road, Unit 3043, Storrs, CT 06269, USA AbbVie, 1 N Waukegan Road, R436 AP9A 2, North Chicago, IL 60064, USA Department of Statistics, University of Connecticut, 215 Glenbrook Road, Unit 4120, Storrs, CT 06269, USA and Department of Bioinformatics and Computational Biology, Division of Quantitative Sciences, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Syst Biol 63:309-21. 2014
    ....
  21. pmc Bayesian spatial transformation models with applications in neuroimaging data
    Michelle F Miranda
    Department of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, U S A
    Biometrics 69:1074-83. 2013
    ..Our STM is able to reveal important brain regions with morphological changes in children with attention deficit hyperactivity disorder. ..
  22. ncbi Bayesian modeling and inference for clinical trials with partial retrieved data following dropout
    Qingxia Chen
    Departments of Biostatistics and Biomedical Informatics, Vanderbilt University, Nashville, TN 37232, U S A
    Stat Med 32:4180-95. 2013
    ..We develop an efficient Markov chain Monte Carlo sampling algorithm. We analyze in detail via the proposed method a real dataset from a clinical trial. Copyright © 2013 John Wiley & Sons, Ltd. ..
  23. ncbi Bayesian inference for multivariate meta-analysis Box-Cox transformation models for individual patient data with applications to evaluation of cholesterol-lowering drugs
    Sungduk Kim
    Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Rockville, MD, U S A
    Stat Med 32:3972-90. 2013
    ..We carry out a detailed analysis of these data by using the proposed methodology. Copyright © 2013 John Wiley & Sons, Ltd. ..
  24. pmc Bayesian gamma frailty models for survival data with semi-competing risks and treatment switching
    Yuanye Zhang
    Novartis Institutes for BioMedical Research, Inc, 220 Massachusetts Avenue, Cambridge, MA, 02139, USA
    Lifetime Data Anal 20:76-105. 2014
    ..A simulation study is conducted to examine the empirical performance of DIC and LPML and as well as the posterior estimates. The proposed method is further applied to analyze data from a colorectal cancer study. ..
  25. ncbi Bayesian dynamic regression models for interval censored survival data with application to children dental health
    Xiaojing Wang
    Google, New York, NY, USA
    Lifetime Data Anal 19:297-316. 2013
    ..5, and that it gradually reduces to one after age 11. These findings were not seen from the existing studies with Cox proportional hazards models. ..
  26. pmc Improving marginal likelihood estimation for Bayesian phylogenetic model selection
    Wangang Xie
    Abbott, 100 Abbott Park, R436 AP9A 2, Abbott Park, IL 60064, USA
    Syst Biol 60:150-60. 2011
    ..We conclude that the greatly increased accuracy of the SS and TI methods argues for their use instead of the HM method, despite the extra computation needed...
  27. pmc A Bayesian proportional hazards regression model with non-ignorably missing time-varying covariates
    Patrick T Bradshaw
    Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Stat Med 29:3017-29. 2010
    ..Our sensitivity analysis showed only slight differences between models with different assumptions on the missing data mechanism yet the complete-case analysis yielded markedly different results...
  28. pmc Choosing among partition models in Bayesian phylogenetics
    Yu Fan
    Department of Ecology and Evolutionary Biology, University of Connecticut
    Mol Biol Evol 28:523-32. 2011
    ..Such dedicated path-based Markov chain Monte Carlo analyses appear to be a cost of estimating marginal likelihoods accurately...
  29. pmc In silico construction of a protein interaction landscape for nucleotide excision repair
    Nancy Tran
    Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Cell Biochem Biophys 53:101-14. 2009
    ..Our analysis offers a computational framework that can be applied to construct landscapes for other biological processes...
  30. pmc A hierarchical model for incomplete alignments in phylogenetic inference
    Fuxia Cheng
    Department of Mathematics, Illinois State University, Normal, IL, USA
    Bioinformatics 25:592-8. 2009
    ..The patterns of missing data typical for EST-derived alignments greatly compromise the accuracy of estimated phylogenies...
  31. pmc Statistical strategies to improve the efficiency of molecular studies of colorectal cancer prognosis
    P Qu
    Cancer Research and Biostatistics CRAB, 1730 Minor Ave Suite 1900, Seattle, WA 98101, USA
    Br J Cancer 99:2001-5. 2008
    ..Using this method, we identified and abandoned potentially uninformative molecular markers in favour of more promising candidates. This approach conserves tissue resources, time, and money, and may be applicable to other studies...
  32. pmc Bayesian variable selection for the Cox regression model with missing covariates
    Joseph G Ibrahim
    Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA
    Lifetime Data Anal 14:496-520. 2008
    ..Monte Carlo methods are developed for computing the DICs for all possible subset models in the model space. A Bone Marrow Transplant (BMT) dataset is used to illustrate the proposed methodology...
  33. pmc A note on the validity of statistical bootstrapping for estimating the uncertainty of tensor parameters in diffusion tensor images
    Ying Yuan
    Department of Statistics and Operations, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    IEEE Trans Med Imaging 27:1506-14. 2008
    ..Our findings raise serious concerns about the use of bootstrap methods to quantify the uncertainty of fiber pathways when those pathways pass through voxels that contain either isotropic tensors, oblate tensors, or multiple tensors...
  34. pmc Bayesian case influence diagnostics for survival models
    Hyunsoon Cho
    Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7420, USA
    Biometrics 65:116-24. 2009
    ..We also present a theoretical relationship between our case-deletion diagnostics and diagnostics based on Cox's partial likelihood. A simulated data example and two real data examples are given to demonstrate the methodology...
  35. ncbi PSA failure following definitive treatment of prostate cancer having biopsy Gleason score 7 with tertiary grade 5
    Abhijit A Patel
    Department of Radiation Oncology, Brigham and Women s Hospital and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    JAMA 298:1533-8. 2007
    ..Yet, the management of men with Gleason score 7 vs 8 or 9 prostate cancer differs...
  36. ncbi Bayesian hierarchical modeling for time course microarray experiments
    Yueh Yun Chi
    Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA
    Biometrics 63:496-504. 2007
    ..The methodology is applied to a mouse model time course experiment to correlate temporal changes in azoxymethane-induced gene expression profiles with colorectal cancer susceptibility...
  37. pmc A statistical analysis of brain morphology using wild bootstrapping
    Hongtu Zhu
    Department of Biostatistics and Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC 27599 7420, USA
    IEEE Trans Med Imaging 26:954-66. 2007
    ..We demonstrate the application of this robust test procedure to the detection of statistically significant differences in the morphology of the hippocampus over time across gender groups in a large sample of healthy subjects...
  38. pmc Defective cell cycle checkpoint functions in melanoma are associated with altered patterns of gene expression
    William K Kaufmann
    Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    J Invest Dermatol 128:175-87. 2008
    ..The results suggest that defects in DNA damage checkpoints may be recognized in melanomas through analysis of gene expression...
  39. ncbi Proximity model for expression quantitative trait loci (eQTL) detection
    Jonathan A L Gelfond
    Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Biometrics 63:1108-16. 2007
    ..We also discuss an extension of the MOM method to model multiple eQTLs, and find that many transcripts are likely associated with more than one eQTL...
  40. ncbi A note on permutation tests for variance components in multilevel generalized linear mixed models
    Garrett M Fitzmaurice
    Harvard Medical School, Boston, MA, USA
    Biometrics 63:942-6. 2007
    ..Results from a simulation study suggest that it is more powerful than tests based on mixtures of chi-square distributions. The proposed test is illustrated using data on the familial aggregation of sleep disturbance...
  41. ncbi Bayesian analysis of generalized odds-rate hazards models for survival data
    Tathagata Banerjee
    Department of Statistics, Calcutta University, Calcutta, 700019, India
    Lifetime Data Anal 13:241-60. 2007
    ..The propriety of the posterior has been established under some mild conditions. A simulation study is conducted and a detailed analysis of the data from a prostate cancer study is presented to further illustrate the proposed methodology...
  42. ncbi Bayesian dynamic models for survival data with a cure fraction
    Sungduk Kim
    Department of Statistics, University of Connecticut, Storrs, CT 06269, USA
    Lifetime Data Anal 13:17-35. 2007
    ..In addition, an efficient reversible jump computational algorithm is developed for carrying out posterior computation. A real data set from a melanoma clinical trial is analyzed in detail to further demonstrate the proposed methodology...
  43. ncbi Semiparametric models for missing covariate and response data in regression models
    Qingxia Chen
    Department of Biostatistics, Vanderbilt University, Nashville, Tennessee 37232, USA
    Biometrics 62:177-84. 2006
    ..Maximum likelihood estimates are then obtained via the EM algorithm. Simulations are given to demonstrate the methodology, and a real data set from a melanoma cancer clinical trial is analyzed using the proposed methods...
  44. pmc A Bayesian hidden Markov model for motif discovery through joint modeling of genomic sequence and ChIP-chip data
    Jonathan A L Gelfond
    Department of Epidemiology and Biostatistics, Mail Code 7933, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229 3900, USA
    Biometrics 65:1087-95. 2009
    ..In simulations and applications to a yeast RAP1 dataset, the proposed method has favorable TFBS discovery performance compared to currently available two-stage procedures in terms of both sensitivity and specificity...
  45. pmc Fixed and random effects selection in mixed effects models
    Joseph G Ibrahim
    Department of Biostatistics, University of North Carolina, McGavran Greenberg Hall, Chapel Hill, North Carolina 27599 7420, USA
    Biometrics 67:495-503. 2011
    ..Simulation studies and a real data set from a Yale infant growth study are used to illustrate the proposed methodology...
  46. pmc Bayesian hierarchical modeling and selection of differentially expressed genes for the EST data
    Fang Yu
    Department of Biostatistics, University of Nebraska Medical Center, Omaha, Nebraska 68198 4350
    Biometrics 67:142-50. 2011
    ..Our new method with the new gene selection criterion is demonstrated via several simulations to have low false negative and false positive rates. A real EST data set is used to motivate and illustrate the proposed method...
  47. pmc Bayesian local influence for survival models
    Joseph G Ibrahim
    Department of Biostatistics, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7420, USA
    Lifetime Data Anal 17:43-70. 2011
    ....
  48. ncbi A new threshold regression model for survival data with a cure fraction
    Sungduk Kim
    Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Rockville, MD 20852, USA
    Lifetime Data Anal 17:101-22. 2011
    ..A real data set from a prostate cancer clinical trial is analyzed in detail to demonstrate the proposed methodology...
  49. pmc Genomewide multiple-loci mapping in experimental crosses by iterative adaptive penalized regression
    Wei Sun
    Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA
    Genetics 185:349-59. 2010
    ..Although our methods are motivated by multiple-loci mapping, they are general enough to be applied to other variable selection problems...
  50. pmc MARM: multiscale adaptive regression models for neuroimaging data
    Hongtu Zhu
    1 Department of Biostatistics, University of North Carolina at Chapel Hill, USA
    Inf Process Med Imaging 21:314-25. 2009
    ..Our simulation studies with known ground truth confirm that the MARM significantly outperforms the voxel-wise methods...
  51. pmc Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging
    Yan Liu
    Department of Genetics, The University of North Carolina School of Medicine, Chapel Hill, USA
    Aging Cell 8:439-48. 2009
    ..These data suggest that p16(INK4a) expression in PBTL is an easily measured, peripheral blood biomarker of molecular age...
  52. pmc Variable selection in the cox regression model with covariates missing at random
    Ramon I Garcia
    Department of Biostatistics, University of North Carolina at Chapel Hill, North Carolina 27599 7420, USA
    Biometrics 66:97-104. 2010
    ..Simulations are performed to evaluate the finite sample performance of the penalty estimates. Also, two lung cancer data sets are analyzed to demonstrate the proposed methodology...
  53. pmc Local influence for generalized linear models with missing covariates
    Xiaoyan Shi
    Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Biometrics 65:1164-74. 2009
    ..Simulation studies are conducted to evaluate our methods, and real datasets are analyzed to illustrate the use of our local influence measures...
  54. ncbi Estimation in regression models for longitudinal binary data with outcome-dependent follow-up
    Garrett M Fitzmaurice
    Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue and Brigham and Women s Hospital, Boston, MA, USA
    Biostatistics 7:469-85. 2006
    ..Finally, we illustrate the main results using data from a longitudinal observational study that explored the cardiotoxic effects of doxorubicin chemotherapy for the treatment of acute lymphoblastic leukemia in children...

Research Grants30

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..
  2. B-cell Biology of Mucosal Immune Protection from SIV Challenge
    Eric Hunter; Fiscal Year: 2013
    ....
  3. Generation of an In Vivo Human Genome Enhancer Dataset
    LEN ALEXANDER PENNACCHIO; Fiscal Year: 2013
    ..The identification of positive signatures of enhancers in vivo is expected to significantly fill our void in gene regulatory annotation of the human genome and to decipher their mutation as a cause of human disease. ..
  4. Systems Analysis of Cardiac Chromatin Structure
    Thomas M Vondriska; Fiscal Year: 2013
    ..The significance to the clinical realm is to provide a mechanistic basis for how the genome is reprogrammed with disease, such that future therapies can target specific chromatin remodeling events. ..
  5. Global Predictions and Tests of Erythroid Regulation
    Yu Zhang; Fiscal Year: 2013
    ....
  6. Jules Stein Eye Institute Core Grant for Vision Research
    Wayne L Hubbell; Fiscal Year: 2013
    ..Support in the form of the Core grant is requested to maintain these Modules through instrument service contracts, and to provide necessary personnel support to assist and train users and provide routine maintenance. ..
  7. Dynamics of nucleosome positioning and the role of chromatin in myogenesis
    DUSTIN EDWARD SCHONES; Fiscal Year: 2013
    ..These studies will lead to a greater understanding of the mechanisms responsible for the organization of nucleosomes across the genome and further elucidate the role of chromatin in the regulation of transcription. ..
  8. Statistical Tools and Methods for Next-Generation Sequencing in Epigenetics
    WILLIAM EVAN JOHNSON; Fiscal Year: 2013
    ..The many useful applications of next-generation sequencing with assure that or well- developed methods will have a broad impact in molecular biology, specifically in transcription regulation, chromatin dynamics, development, and cancer. ..
  9. Interrogating Epigenetic Changes in Cancer Genomes
    Tim H M Huang; Fiscal Year: 2013
    ..abstract_text> ..
  10. The role of macroH2A variants in cancer and senescence
    Matthew J Gamble; Fiscal Year: 2013
    ..1 target genes. PARP-1 is a current therapeutic target in cancer treatment, highlighting the need to understand the functional connection between these two cancer-relevant molecules. ..
  11. Mechanistic Pharmacology of Anti-Mitotics and Apoptosis Regulation
    Timothy J Mitchison; Fiscal Year: 2013
    ..In aim 4 we will pursue several approaches towards translating mechanistic understanding from aims 1-3 into improved patient care. ..
  12. DECIPHERING ENZYME SPECIFICITY
    John A Gerlt; Fiscal Year: 2013
    ..The goals of this Program Project extend the contribution of the Protein Structure Initiative funded by NIGMS that seeks to obtain structures for proteins of unknown function that will allow reliable homology modeling. ..
  13. Transcriptional elongation and splicing in human genes in situ
    Richard A Padgett; Fiscal Year: 2013
    ..These studies will advance our understanding of human gene expression which is of major relevance to both normal and pathological cell growth and development. ..